TMEM55B promotes anterograde transport and distal axonal distribution of LAMP1-positive organelles

Probably not a substantial claim.

The spatio-temporal distribution of lysosomes depends on active transport driven by the anterograde and retrograde motors kinesin and dynein.

“Their spatio-temporal distribution depends on active transport driven by the anterograde-and retrograde motors kinesin and dynein, respectively (Bonifacino and Neefjes, 2017;Saftig and Puertollano, 2021).”

• cites Bonifacino and Neefjes, 2017 sourceSupported
• cites Saftig and Puertollano, 2021Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Axonal endo-/lysosomal organelles pathologically accumulate in axonal spheroids.

“The relevance of axonal endo-/lysosomal organelles is further highlighted by the fact that they pathologically accumulate in axonal spheroids.”

• cites Cataldo and Nixon, 1990 sourceNot checked — no full text of the source
• cites Lie et al., 2021 sourceSupported

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The great majority of the total pool of lysosomes in neurons is localized in the somatodendritic compartment.

“the great majority of the total pool of lysosomes in neurons is localized in the somatodendritic compartment (Becker et al., 1960)”

• cites Becker et al., 1960 sourcePartly supported

  The figure captions (p. 654) describe numerous lysosomes in neuronal cell bodies and dendrites, and the Results (p. 657) say lysosomes are readily seen in dendrites. But the paper says their presence in axons is difficult to establish and does not determine what fraction of the total neuronal lysosome pool is somatodendritic. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Lysosomal function is vital for the proper function and survival of post-mitotic neurons.

“Their function is vital for the proper function and survival of post-mitotic neurons, and, not surprisingly, dysregulation of lysosomal degradative pathways is linked to various neurodegenerative disorders (Wallings et al., 2019;Wang et al., 2018).”

• cites Wallings et al., 2019 sourceSupported
• cites Wang et al., 2018Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Lysosomes fuse with autophagosome in the distal axon, and they mature on the way back to the soma.

“Lysosomes fuse with autophagosome in the distal axon, and they mature on the way back to the soma (Maday et al., 2012).”

• cites Maday et al., 2012 sourcePartly supported

  In Results and discussion, under “Maturation of autophagosomes moving distally to proximally along the axon,” the paper reports maturation during transport toward the soma. It describes fusion near the distal tip as suggested by its observations and says the fusion partner may be a late endosome and/or a lysosome; it does not establish the claim’s unqualified statement that lysosomes fuse there. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Binding of either dynein or kinesin-1 to JIPs is not exclusive and is non-competitive.

“Binding of either dynein or kinesin-1 to JIPs is not exclusive and is non-competitive (Vilela et al., 2026).”

• cites Vilela et al., 2026 sourceSupported

Probably not a substantial claim. The paper’s conclusions may not depend on it.

TMEM55B plays a critical role in the microtubule-dependent retrograde positioning of lysosomes upon overexpression and knockdown in non-neuronal cell-based models.

“TMEM55B plays a critical role in the microtubule-dependent retrograde positioning of lysosomes upon overexpression and knockdown (KD) in non-neuronal cell-based models (Willett et al., 2017).”

• cites Willett et al., 2017 sourceSupported

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

JIP4 is a large scaffold that binds both dynein and kinesin-1.

“JIP4 is a large scaffold that binds both dynein and, notably, also kinesin-1, which mediates anterograde organelle transport (Celestino et al., 2022;Montagnac et al., 2009;Nguyen et al., 2005;Verhey et al., 2001;Vilela et al., 2019).”

• cites Celestino et al., 2022 sourcePartly supported

  The Results section (page unavailable) reports that JIP4’s RH1 domain binds the dynein light intermediate chain. The paper’s kinesin-1 binding experiments concern JIP3, not JIP4, so this source does not establish the claimed JIP4–kinesin-1 interaction. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites Montagnac et al., 2009 sourcePartly supported

  The Results describe JIP4 as a scaffolding protein and show that it binds kinesin-1. They show JIP4 interacting with the dynactin complex, however, not binding dynein itself; the dynein observation in the retrieved Results concerns JIP3. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites Nguyen et al., 2005 sourcePartly supported

  The Discussion (page unavailable) identifies JIP-4 as a scaffolding protein and says it interacts with kinesin light chain 1, a component of kinesin-1. The passages found do not say that JIP-4 binds dynein, so the claim of binding both motors is only partially supported. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

This phosphatase function was later challenged, and phosphatase activity could not be reproduced.

“This function was later challenged (Pal et al., 2023;Willett et al., 2017), and phosphatase activity could not be reproduced.”

• cites Pal et al., 2023 sourceSupported
• cites Willett et al., 2017 sourceSupported

Probably not a substantial claim. The paper’s conclusions may not depend on it.

JIP3 can induce kinesin activity in vitro.

“Accordingly, JIP3 (a paralog of JIP4) can induce kinesin activity in vitro (Vilela et al., 2026;Watt et al., 2015), and JIP3/4 can also activate dynein (Cason and Holzbaur, 2023).”

• cites Vilela et al., 2026 sourceSupported
• cites Watt et al., 2015 sourceSupported

Probably not a substantial claim. The paper’s conclusions may not depend on it.

KD of JIP4 drives lysosomes into the cell's periphery.

“Likewise, the KD of JIP4 drives lysosomes into the cell's periphery (Willett et al., 2017).”

• cites Willett et al., 2017 sourceSupported

It may state two separate claims as one.

TMEM55B recruits the cytosolic scaffold protein JIP4, which serves as a platform for both microtubule motor proteins dynein and kinesin-1.

“TMEM55B recruits the cytosolic scaffold protein JIP4 (Willett et al., 2017), which serves as a platform for both microtubule motor proteins dynein and kinesin-1.”

• cites Willett et al., 2017 sourceSupported

Probably not a substantial claim. It may state two separate claims as one.

JIP4 binds dynein/dynactin and mediates retrograde lysosomal transport.

“JIP4 binds dynein/dynactin and mediates retrograde lysosomal transport (Willett et al., 2017).”

• cites Willett et al., 2017 sourceSupported

Probably not a substantial claim. The paper’s conclusions may not depend on it.

TMEM55A overexpression does not affect lysosomal positioning.

“TMEM55A overexpression does not affect lysosomal positioning (Willett et al., 2017), suggesting it may have functions independent of lysosomal positioning.”

• cites Willett et al., 2017 sourceSupported

Probably not a substantial claim.

The number and composition of lysosomes differ between the proximal axon and the distal axon.

“The entry of cargo (including lysosomes) into the axon at the proximal axon and the axon initial segment (AIS) is tightly regulated, and the number and composition of lysosomes differ between the proximal axon and the distal axon (Farias et al., 2017b;Ozkan et al., 2021).”

• cites Farias et al., 2017bNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Ozkan et al., 2021 sourceCould not verify

  The Results section, “ER shape regulates lysosome availability in the axon” (page unavailable), counts lysosomes in a proximal-axon segment and describes their distribution along the axon. A search for proximal-versus-distal comparisons found no passage establishing that lysosome number or composition differs between those regions. (LLM, conf=0.72)

  Experimental — accuracy not yet measured

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Kinesin-1 and kinesin-3 are the principal anterograde motors mediating the transport of lysosomes.

“Kinesin-1 and kinesin-3 are the principal anterograde motors mediating the transport of lysosomes (Guardia et al., 2016).”

• cites Guardia et al., 2016 sourcePartly supported

  The Results section identifies kinesin-1 KIF5B and kinesin-3 KIF1B as the most important kinesins for outward lysosome movement in HeLa cells. The Discussion also says kinesin-1 and -3 drive lysosome movement toward the cell periphery. The claim omits the HeLa-cell qualification on the paper’s finding that these are the principal motors. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Alternative adaptor mechanisms on lysosomes for kinesins include the scaffolds JIP3 and JIP4.

“Alternative adaptor mechanisms on lysosomes for kinesins have been described, among the scaffolds c-Jun NH2-terminal kinase (JNK)-interacting protein 3 (JIP3) and JIP4 (Vilela et al., 2026;Watt et al., 2015).”

• cites Vilela et al., 2026 sourceSupported
• cites Watt et al., 2015 sourcePartly supported

  The Discussion (page not available) shows that the scaffold JIP3 activates kinesin-1 motility through interactions with its light and heavy chains. Our copy does not establish this mechanism on lysosomes or describe JIP4 as a kinesin adaptor; lysosomes appear in the title of a cited work in the References, not in this paper’s reported findings. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Probably not a substantial claim.

The entry of cargo (including lysosomes) into the axon at the proximal axon and the axon initial segment (AIS) is tightly regulated.

“The entry of cargo (including lysosomes) into the axon at the proximal axon and the axon initial segment (AIS) is tightly regulated, and the number and composition of lysosomes differ between the proximal axon and the distal axon (Farias et al., 2017b;Ozkan et al., 2021).”

• cites Farias et al., 2017bNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Ozkan et al., 2021 sourceSupported

It may state two separate claims as one.

TBC1D9B is a TMEM55B-binder that acts as a GTPase-activating protein (GAP) for ARL8B.

“among them JIP4 and TBC1D9B, which we found independently as a TMEM55B-binder that acts as a GTPase-activating protein (GAP) for ARL8B (Duhay et al., 2026)”

• cites Duhay et al., 2026 sourceSupported

It may state two separate claims as one.

UNC-16-deficient worms show a clearly aggravated phenotype, including uncoordinated movement, which is not the case for Y71H2AM.2(null) worms.

“However, UNC-16-deficient worms show a clearly aggravated phenotype, including uncoordinated movement, which is not the case for Y71H2AM.2(null)worms”

• cites Celestino et al., 2022 sourcePartly supported

  The Results section, “Dynein light intermediate chain binding is essential for UNC-16 function in vivo,” reports that unc-16 loss-of-function animals are locomotion deficient, supporting the uncoordinated-movement part of the claim. Our copy does not report a phenotype for Y71H2AM.2(null) worms, so it does not support the comparison. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites Edwards et al., 2015 sourceNot checked — no full text of the source
• cites Edwards et al., 2013 sourcePartly supported

  The Results report that three unc-16 mutants had sluggish locomotion rates of about 15% of wild type, supporting a substantial movement defect. The paper does not report a phenotype for Y71H2AM.2(null) worms, so it does not support the comparison between the mutants. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

DA and DB motor neurons drive backward and forward locomotion, respectively.

“It has been demonstrated that DA and DB motor neurons drive backward and forward locomotion, respectively (Haspel et al., 2010;Wen et al., 2012).”

• cites Haspel et al., 2010 sourceSupported
• cites Wen et al., 2012 sourceSupported

It may state two separate claims as one.

JIP4 deficiency alone has a strong effect in neurons, given that JIP3 seems to be even more critical for axonal transport, and they have at least partially redundant functions.

“It is interesting that JIP4 deficiency (likely in complex with TMEM55B) alone has such a strong effect in neurons, given that JIP3 seems to be even more critical for axonal transport, and they have been shown to have at least partially redundant functions (Gowrishankar et al., 2021).”

• cites Gowrishankar et al., 2021 sourceSupported

It may state two separate claims as one.

In contrast to wildtype worms, in which lysosomes are excluded from the axon and CTNS-1::mCherry labeling was predominantly confined to motor neuron somata, with weaker signals detected in dendrites, adult Y71H2AM.2(null) worms exhibited extensive axonal CTNS-1::mCherry labeling under steady-state conditions.

“In contrast to wildtype worms, in which lysosomes are excluded from the axon (Niwa et al., 2017) and CTNS-1::mCherry labeling was predominantly confined to motor neuron somata, with weaker signals detected in dendrites, adult Y71H2AM.2(null)worms exhibited extensive axonal CTNS-1::mCherry labeling under steady-state conditions (Figure 6C).”

• cites Niwa et al., 2017 sourceSupported

• AssumptionRests on an assumption: CTNS-1::mCherry is a specific marker for lysosomes in C. elegans.

It may state two separate claims as one.

The observation of clustered lysosomes was not restricted to cortical neurons but was also observed in other neuronal populations, such as hippocampal neurons, and was most pronounced in thalamic neurons.

“The observation of clustered lysosomes was not restricted to cortical neurons but was also observed in other neuronal populations, such as hippocampal neurons, and was most pronounced in thalamic neurons (Figure 1E).”

It may state two separate claims as one.

Only a few transcripts showed fold changes >1.5-fold; these included a typical activated microglial signature, with Gpnmb, Lgals3, Ccl3, C3, and Cd68 as differentially expressed transcripts.

“Only a few transcripts showed fold changes >1.5-fold; these included a typical activated microglial signature, with Gpnmb, Lgals3, Ccl3, C3, and Cd68 as differentially expressed transcripts.”

It may state two separate claims as one.

No statistically significant differences compared with age-matched wildtype mice could be determined in grip strength, rotarod performance, gait symmetry, or spatial gait parameters.

“No statistically significant differences compared with age-matched wildtype mice could be determined in grip strength, rotarod performance, gait symmetry, or spatial gait parameters (Supplemental Figure 4A-C).”

It may state two separate claims as one.

JIP4 shows a similar tissue expression to TMEM55B with robust expression in the brain and no differences between wildtype and Tmem55b -/- KO mice.

“Interestingly, JIP4 shows a similar tissue expression to TMEM55B with robust expression in the brain (Supplemental and no differences between wildtype and Tmem55b -/-KO mice (Figure 3B)”

It may state two separate claims as one.

Coimmunofluorescence of LAMP1 with the lysosomal hydrolase Cathepsin D revealed the presence of this soluble enzyme in a subpopulation of LAMP1+ organelles, and the tubular structures were devoid of CTSD immunoreactivity.

“Coimmunofluorescence of LAMP1 with the lysosomal hydrolase Cathepsin D (CTSD) revealed the presence of this soluble enzyme in a subpopulation of LAMP1 + organelles, and remarkably, the tubular structures were devoid of CTSD immunoreactivity (Figure 1H).”

• AssumptionRests on an assumption: LAMP1 is a specific marker for lysosomes.

It may state two separate claims as one.

TMEM55B is expressed in different organs, with the highest protein levels among the analyzed tissues in the testis, the brain, followed by the spleen, the lung, and the thymus, and very low relative expression in the kidney and the liver.

“TMEM55B is expressed in different organs, with the highest protein levels among the analyzed tissues in the testis, the brain, followed by the spleen, the lung, and the thymus, and very low relative expression in the kidney and the liver (Supplemental Figure 1A).”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

We could not unambiguously identify the native Y71H2AM.2 promoter within a 4-kb genomic region upstream of the 5' UTR, which indicates that the native Y71H2AM.2 promoter might be located outside the tested range.

“However, we could not unambiguously identify it, which indicates that the native Y71H2AM.2 promoter might be located outside the tested range.”

It may state two separate claims as one.

High-resolution Airyscan microscopy of cortical sections revealed an increase in the size of LAMP1+ lysosomes in cortical neurons from Tmem55b -/- KO mice of 0.6-0.7 μm compared to 0.48-0.5 μm, with enlarged lysosomes >1.5 μm only seen in neurons of Tmem55b -/- KO mice.

“High-resolution Airyscan microscopy of cortical sections revealed an increase in the size of LAMP1 + lysosomes in cortical neurons from Tmem55b -/-KO mice of 0.6 -0.7 µm compared to 0.48 -0.5 µm, with enlarged lysosomes >1.5 µm only seen in neurons of Tmem55b -/-KO mice.”

• AssumptionRests on an assumption: LAMP1 is a specific marker for lysosomes.

It may state two separate claims as one.

Analysis of animals ranging from 6 weeks to 1.5 years old revealed that the redistribution was age-independent and was an early phenotypic feature.

“Analysis of animals ranging from 6 weeks to 1.5 years old revealed that the redistribution was ageindependent and was an early phenotypic feature.”

It may state two separate claims as one.

The total number of LAMP1-GFP compartments was unchanged in the proximal axon, significantly reduced in the mid-axon, and even more strongly reduced in the distal axon.

“The total number of LAMP1-GFP compartments was unchanged in the proximal axon, significantly reduced in the mid-axon, and even more strongly reduced in the distal axon (Supplemental Figure 6B).”

• AssumptionRests on an assumption: LAMP1 is a specific marker for lysosomes.

It may state two separate claims as one.

While p62-aggregates were abundant in a distinct layer of the cortex, major parts of the brain lacked p62 pathology.

“While p62-aggregates were abundant in a distinct layer of the cortex, major parts of the brain lacked p62 pathology.”

It may state two separate claims as one.

TMEM55B and the lysosomal marker LAMP1 show prominent co-localization in cortical neurons in situ, confirming predominantly lysosomal localization at endogenous levels.

“Furthermore, a co-immunofluorescence experiment of TMEM55B and the lysosomal marker LAMP1 revealed prominent co-localization in cortical neurons in situ, confirming predominantly lysosomal localization at endogenous levels (Supplemental Figure 1D).”

• AssumptionRests on an assumption: LAMP1 is a specific marker for lysosomes.

It may state two separate claims as one.

CRISPR/Cas9-mediated Tmem55b -/- KO mice in a C57/Bl6N background were viable, born at the expected Mendelian ratios, and survived to adulthood without increased mortality or apparent gross morphological abnormalities.

“In contrast to a previous report, in which early embryonic lethality was reported upon Tmem55b gene disruption (Hashimoto et al., 2018), CRISPR/Cas9-mediated Tmem55b -/-KO mice in a C57/Bl6N background were viable/born at the expected Mendelian ratios and survived to adulthood without increased mortality or any apparent gross morphological abnormalities (Supplemental Figure 2F).”

• cites Hashimoto et al., 2018Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

The number of stationary lysosomes was similar in the mid-axon but significantly reduced in the distal axon of TMEM55B shRNA-treated neurons.

“The number of stationary lysosomes was similar in the mid-axon but significantly reduced in the distal axon of TMEM55B shRNA-treated neurons.”

It may state two separate claims as one.

Bulk RNA sequencing of whole-brain RNA from adult wildtype and Tmem55b -/- KO mice revealed a clear separation of both genotype groups by principal component analysis and subtle transcriptional upregulation of a number of lysosomal genes.

“Transcriptome analysis of whole-brain RNA from adult wildtype and Tmem55b -/-KO mice by bulk RNA sequencing revealed a clear separation of both genotype groups by principal component analysis (Supplemental Figure 3A) and revealed subtle transcriptional upregulation of a number of lysosomal genes (Figure 1D)”

It may state two separate claims as one.

Tmem55a/b double KO mice show retarded growth and premature death.

“While Tmem55a KO mice show no phenotype at all, double KO mice for Tmem55b and the close paralog Tmem55a show retarded growth and premature death, consistent with partially overlapping or additive functions of TMEM55A and TMEM55B.”

It may state two separate claims as one.

Tmem55a -/- KO mice were viable and showed no obvious phenotype.

“Tmem55a -/-KO mice were viable and showed no obvious phenotype.”

• AssumptionRests on an assumption: The Tmem55a -/- KO mice are full knockouts.

It may state two separate claims as one.

Tmem55a/Tmem55b double KO mice exhibit retarded growth and premature lethality.

“Tmem55a/Tmem55b -/--/-(Tmem55a/b -/--/-) double KO mice exhibit retarded growth and premature lethality.”

It may state two separate claims as one.

Immunohistochemical survey of the Tmem55a/b double KO and a direct comparison with the single KO mice revealed an additional increase in the size of lysosomes, more clumpy aggregation of lysosomes in the area of the PAEZ, and a further increase in the amount of deposited lipofuscin.

“Immunohistochemical survey of the Tmem55a/b double KO and a direct comparison with the single KO mice revealed an additional increase in the size of lysosomes, more clumpy aggregation of lysosomes in the area of the PAEZ, and a further increase in the amount of deposited lipofuscin (Figure 8E).”

It may state two separate claims as one.

Analysis of crawling activity, quantified by track length on agarose plates, revealed that neuronal expression of mTMEM55B fully rescued the locomotor deficit of Y71H2AM.2(null) worms at day 3 and resulted in a clear trend toward normalization of locomotor activity at later ages.

“Analysis of crawling activity, quantified by track length on agarose plates, revealed that neuronal expression of mTMEM55B fully rescued the locomotor deficit of Y71H2AM.2(null)worms at day 3 and resulted in a clear trend toward normalization of locomotor activity at later ages (Figure 7C).”

It may state two separate claims as one.

The velocities of CTNS-1::mCherry-positive lysosomes were reduced during anterograde transport but remained unchanged during retrograde transport.

“In addition, the velocities of CTNS-1::mCherry-positive lysosomes were reduced during anterograde transport but remained unchanged during retrograde transport.”

• AssumptionRests on an assumption: CTNS-1::mCherry is a specific marker for lysosomes in C. elegans.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Tmem55b -/- KO mice tended to perform better than wildtype controls on the rotarod, independent of trials.

“Tmem55b -/-KO mice tended to perform better than wildtype controls (F = 3.3, p = 0.08), independent of trials (F = 0.2, p = 0.92).”

It may state two separate claims as one.

Aged Tmem55b -/- mice show lipofuscin deposition, p62 aggregates, and mild white-matter microgliosis.

“Aged Tmem55b -/-mice show lipofuscin deposition, p62 aggregates, and mild white-matter microgliosis.”

It may state two separate claims as one.

We observed an increased mortality rate that did not occur at a specific age but rather appeared sporadically.

“We observed an increased mortality rate that did not occur at a specific age but rather appeared sporadically (Figure 8C).”

It may state two separate claims as one. The quote only partly states this claim.

Tmem55a/b -/- dKO neurons showed larger, more densely clustered lysosomes in the PAEZ, but neuroinflammation was not exacerbated in the spinal cord.

“Neurons showed larger, more densely clustered lysosomes in the PAEZ, but neuroinflammation was not exacerbated in the spinal cord.”

It may state two separate claims as one.

TMEM55B deficiency in mammalian neurons causes accumulation of LAMP1-positive organelles at the PAEZ/AIS region and depletion from distal axons.

“Although TMEM55B deficiency in mammalian neurons caused an accumulation of LAMP1positive organelles at the PAEZ/AIS region and depletion from distal axons”

It may state two separate claims as one.

Knockout of the TMEM55B-ortholog Y71H2AM.2 in C. elegans leads to the accumulation of lysosomes in the axon and locomotion deficits.

“Knockout of the TMEM55B-ortholog Y71H2AM.2 in C. elegans leads to the accumulation of lysosomes in the axon and locomotion deficits.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

TMEM55B is highly expressed in neurons of the mouse brain.

“TMEM55B is highly expressed in neurons of the mouse brain.”

It may state two separate claims as one.

Lysosomal markers and the autophagy marker LC3-II are unchanged in Tmem55b -/- KO mice.

“Lysosomal markers and the autophagy marker LC3-II are unchanged in Tmem55b -/-KO mice.”

It may state two separate claims as one.

Neuron-specific re-expression of murine TMEM55B in C. elegans Y71H2AM.2(null) animals rescues abnormal lysosomal distribution and locomotor defects.

“Neuron-specific re-expression of murine TMEM55B in C. elegans Y71H2AM.2(null)animals rescues abnormal lysosomal distribution and locomotor defects.”

It may state two separate claims as one.

Analysis of individual movement segments revealed that the loss of Y71H2AM.2 significantly reduced the run length of CTNS-1::mCherry-positive organelles in both anterograde and retrograde directions, with a more pronounced effect on anterograde transport.

“Notably, analysis of individual movement segments revealed that the loss of Y71H2AM.2 significantly reduced the run length of CTNS-1::mCherry-positive organelles in both anterograde and retrograde directions, with a more pronounced effect on anterograde transport.”

• AssumptionRests on an assumption: CTNS-1::mCherry is a specific marker for lysosomes in C. elegans.

It may state two separate claims as one.

Microgliosis in the white matter of the spinal cord of Tmem55a/b -/- dKO mice was comparable with Tmem55b -/- KO mice and again most pronounced around the ventral medial fissure.

“Microgliosis in the white matter of the spinal cord of Tmem55a/b -/ -/--dKO mice was comparable with Tmem55b -/-KO mice and again most pronounced around the ventral medial fissure (Figure 8F).”

It may state two separate claims as one.

Y71H2AM.2(null) animals expressing mTMEM55B were viable and exhibited a lifespan comparable to that of N2 wildtype animals.

“By contrast, Y71H2AM.2(null)animals expressing mTMEM55B were viable and exhibited a lifespan comparable to that of N2 wildtype animals.”

It may state two separate claims as one.

Tmem55a/b -/- dKO mice show reduced weight gain and do not make up the weight as they aged.

“The Tmem55a/b -/--/-dKO mice showed reduced weight gain; surprisingly, they did not make up the weight as they aged.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

More recent work shows compelling evidence for an important physiological function of lysosomes or related LAMP1+ organelles in the axon.

“more recent work shows compelling evidence for an important physiological function of lysosomes or related LAMP1 + -organelles in the axon (Adnan et al., 2020;Bonifacino and Neefjes, 2017;Cason et al., 2022;Cheng et al., 2018;De Pace et al., 2020;Farfel-Becker et al., 2019;Farias et al., 2015;Farias et al., 2017a;Roney et al., 2022;Winckler et al., 2018).”

• cites Adnan et al., 2020 sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites Bonifacino and Neefjes, 2017 sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites Cason et al., 2022Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Dysregulation of lysosomal degradative pathways is linked to various neurodegenerative disorders.

“Their function is vital for the proper function and survival of post-mitotic neurons, and, not surprisingly, dysregulation of lysosomal degradative pathways is linked to various neurodegenerative disorders (Wallings et al., 2019;Wang et al., 2018).”

• cites Wallings et al., 2019 sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites Wang et al., 2018Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

These data indicate that the mislocalization of lysosomes has no major influence on neuronal function and only mildly alters behavior.

“In summary, these data indicate that the mislocalization of lysosomes has no major influence on neuronal function and only mildly alters behavior.”

• AssumptionRests on an assumption: The behavioral tests used are sensitive enough to detect relevant neuronal dysfunction in Tmem55b -/- KO mice.

It may state two separate claims as one.

Our findings extend the knowledge of TMEM55B-dependent lysosomal positioning and reveal a function in bidirectional retrograde and anterograde transport.

“Importantly, our findings extend the knowledge of TMEM55B-dependent lysosomal positioning and reveal a function in bidirectional retrograde and, notably, anterograde transport.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

TMEM55B binds additional interaction partners besides JIP4.

“Besides JIP4, TMEM55B binds additional interaction partners (mostly regulating endo-/ lysosomal function), suggesting that it may act more generally as a scaffold (Damme and Kummel, 2026;Waschbusch et al., 2026).”

• cites Damme and Kummel, 2026Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Waschbusch et al., 2026Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim.

Only cargo bound to kinesins can pass the PAEZ.

“Consequently, only cargo bound to kinesins can pass the PAEZ (Farias et al., 2015).”

• cites Farias et al., 2015Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Animals that were lost during the experiment were censored from the analysis.

“Animals that were lost during the experiment were censored from the analysis.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The location of the novel and familiar object was counterbalanced across the experimental groups.

“The location of the novel and familiar object was counterbalanced across the experimental groups.”

Probably not a substantial claim.

The region proximal to the AIS, the pre-axonal exclusion zone (PAEZ), governs cargo entry into the axon, including lysosomes.

“more recent work, however, suggests that the region proximal to the AIS, the so-called pre-axonal exclusion zone (PAEZ), governs cargo entry into the axon, including lysosomes (Farias et al., 2015).”

• cites Farias et al., 2015Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim.

Identical imaging parameters were used across experimental groups within each experiment to enable direct comparison of fluorescence patterns.

“Identical imaging parameters were used across experimental groups within each experiment to enable direct comparison of fluorescence patterns.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Mutant strains and N2 wildtype controls were assayed in parallel to minimize potential effects of environmental variation.

“Mutant strains and N2 wildtype controls were assayed in parallel to minimize potential effects of environmental variation.”

Probably not a substantial claim.

Homozygosity of the mutant allele was confirmed by PCR amplification of genomic DNA and/or sequencing of the resulting PCR products.

“Homozygosity of the mutant allele was confirmed by PCR amplification of genomic DNA and/or sequencing (Eurofins Genomics GmbH) of the resulting PCR products.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

TMEM55A and TMEM55B were initially identified as PI(4,5)P2 4-phosphatase.

“TMEM55A and TMEM55B were initially identified as phosphatidylinositol (PI)(4,5)P 2 4-phosphatase (Ungewickell et al., 2005).”

• cites Ungewickell et al., 2005Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The comparatively low conservation of the remaining N-terminal sequence suggests that this region may confer distinct functional properties on TMEM55A and TMEM55B.

“The comparatively low conservation of the remaining N-terminal sequence suggests that this region may confer distinct functional properties on TMEM55A and TMEM55B.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

All behavioral tests were performed under standardized conditions.

“All behavioral tests were performed under standardized conditions with female wildtype and Tmem55b -/-mice.”

Probably not a substantial claim. The authors may not put it forward as true. It may state two separate claims as one.

Polarized cargo sorting at the PAEZ is microtubule-based and depends on the differential acquisition of microtubule motors that mediate selective transport into the axon.

“A model was proposed in which polarized cargo sorting at the PAEZ is microtubule-based and depends on the differential acquisition of microtubule motors that mediate selective transport into the axon (Farias et al., 2015).”

• cites Farias et al., 2015Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim.

Founder mice harboring an eight-bp deletion in Tmem55a and a four-bp deletion in Tmem55b, each leading to frameshift mutations, were selected for breeding.

“Founder mice harboring an eight-bp deletion within the second exon of Tmem55a and a four-bp deletion in exon two of Tmem55b, each leading to frameshift mutations, were selected for further breeding.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

TMEM55A may have functions independent of lysosomal positioning.

“TMEM55A overexpression does not affect lysosomal positioning (Willett et al., 2017), suggesting it may have functions independent of lysosomal positioning.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Locomotion tracks from at least 10 individual animals per condition were assessed in each experiment, and at least three independent experiments were performed.

“Locomotion tracks from at least 10 individual animals per condition were assessed in each experiment, and at least three independent experiments were performed.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Each lysate sample was incubated and measured without the corresponding substrate as a negative control.

“Each lysate sample was also incubated and measured without the corresponding substrate as a negative control/substrate blank.”

Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. It may state two separate claims as one.

Bulk membrane fractionation does not resolve lysosome-specific pools; a lysosome-specific approach would be required to determine whether TMEM55B specifically affects JIP4 recruitment to lysosomal membranes.

“Of note, bulk membrane fractionation does not resolve lysosome-specific pools; a lysosome-specific approach (e.g., Lyso-IP) would be required to determine whether TMEM55B specifically affects JIP4 recruitment to lysosomal membranes.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Both shRNAs used for TMEM55B knockdown have been validated using immunofluorescence in this study.

“Both shRNAs have been validated using immunofluorescence in this study.”

Probably not a substantial claim.

Genome editing in founder mice was confirmed by PCR amplification.

“Genome editing was confirmed by PCR amplification in the resulting founder mice.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

At least three independent experiments were performed for each strain.

“At least three independent experiments were performed for each strain.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

For all locomotion assays, mutant and transgenic strains were analyzed in parallel with their respective control strains on the same day and using plates prepared from the same batch and seeded with Escherichia coli OP50.

“For all locomotion assays, mutant and transgenic strains were analyzed in parallel with their respective control strains (N2 wildtype animals or non-transgenic siblings) on the same day and using plates prepared from the same batch and seeded with Escherichia coli OP50.”

The quote only partly states this claim.

LAMP1+ vesicles critically depend on the TMEM55B and JIP4 complex.

“The conditional KO of Jip4 resembles the phenotype resulting from TMEM55B deficiency in mice, suggesting at least partial critical dependence of LAMP1 + -vesicles on the TMEM55B and JIP4 complex.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

For all constructs generated from PCR-amplified fragments, the integrity of the cloned sequence was verified, and only clones containing no mutations within the sequence of interest were used.

“For all constructs generated from PCR-amplified fragments, the integrity of the cloned sequence was verified, and only clones containing no mutations within the sequence of interest were used.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

JIP3/4 can also activate dynein.

“Accordingly, JIP3 (a paralog of JIP4) can induce kinesin activity in vitro (Vilela et al., 2026;Watt et al., 2015), and JIP3/4 can also activate dynein (Cason and Holzbaur, 2023).”

• cites Cason and Holzbaur, 2023 sourceNot checked yet

Probably not a substantial claim.

Imaging settings were kept constant across all experimental conditions.

“Imaging settings were kept constant across all experimental conditions.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

More recent studies support a PI(4,5)P2 4-phosphatase function for TMEM55A.

“More recent studies, however, support a PI(4,5)P 2 4-phosphatase function for TMEM55A (Liu et al., 2025;Morioka et al., 2018).”

• cites Liu et al., 2025 sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

• cites Morioka et al., 2018 sourceNot checked — no full text of the source

It may state two separate claims as one.

These data support the conclusion that TMEM55B and JIP4 act in a shared pathway regulating lysosomal positioning in forebrain neurons, but that JIP4 fulfills other functions independent of TMEM55B-mediated lysosomal positioning.

“In summary, these data support the conclusion that TMEM55B and JIP4 act in a shared pathway regulating lysosomal positioning in forebrain neurons, but that JIP4 fulfills other functions independent of TMEM55B-mediated lysosomal positioning.”

It may state two separate claims as one.

The full KO was validated at the protein level by analyzing tissue lysates from the brain and different organs by immunoblot and by immunohistochemistry on brain sections with a TMEM55B-specific antibody.

“The full KO was validated at the protein level by analyzing tissue lysates from the brain and different organs by immunoblot (Figure 1A, Supplemental Figure 2G) and by immunohistochemistry on brain sections (Figure 1B) with a TMEM55B-specific antibody.”

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

TMEM55B can undergo reversible phosphorylation and is S-palmitoylated.

“TMEM55B can undergo reversible phosphorylation and is S-palmitoylated (Rudnik et al., 2022;Takemasu et al., 2019), suggesting a complex regulation of the protein's function by posttranslational modifications.”

• cites Rudnik et al., 2022Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Takemasu et al., 2019 sourceNot checked — no full text of the source

It may state two separate claims as one.

Impaired endolysosomal degradation and lysosomal dysfunction are implicated in Tmem55b -/- KO mice.

“thereby indirectly implicating impaired endolysosomal degradation and lysosomal dysfunction.”

Probably not a substantial claim.

For KD experiments, only cells displaying continuous labeling of the cytosolic fluorescent protein along the somatodendritic and axonal domains were imaged.

“For KD experiments, only cells displaying continuous labeling of the cytosolic fluorescent protein (fill) along the somatodendritic and axonal domains were imaged.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Both TMEM55A and TMEM55B are localized in late endosomes and lysosomes.

“Notably, both are localized in late endosomes and lysosomes (Ungewickell et al., 2005).”

• cites Ungewickell et al., 2005Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The high expression of TMEM55B in neurons is compatible with their high demand for proteins related to organelle trafficking in neurites.

“compatible with their high demand for proteins related to organelle trafficking in neurites.”

It may state two separate claims as one.

These data reveal that TMEM55B is critical for the normal distribution of lysosomes in the axon, supporting our in situ data in mice.

“In conclusion, these data reveal that TMEM55B is critical for the normal distribution of lysosomes in the axon, supporting our in situ data in mice.”

It may state two separate claims as one.

Our analyses revealed only minor and late-onset impairment of autophago-/lysosomal degradation and mild signs of microgliosis in white matter tracts, suggesting axonal insult and damage.

“In summary, our analyses revealed only minor and late-onset impairment of autophago-/lysosomal degradation and mild signs of microgliosis in white matter tracts, suggesting axonal insult and damage.”

It may state two separate claims as one.

These data provide evidence of partial, but not fully overlapping, functions among different adaptor machineries.

“These data also highlight the complexity among different adaptor machineries, providing evidence of partial, but not fully overlapping, functions.”

It may state two separate claims as one.

In the absence of TMEM55B, lysosomes accumulate at the axon entry zone, fail to efficiently engage the anterograde transport machinery, and are consequently depleted from distal axonal regions.

“In the absence of TMEM55B, lysosomes accumulate at the axon entry zone, fail to efficiently engage the anterograde transport machinery, and are consequently depleted from distal axonal regions.”

• AssumptionRests on an assumption: The proximal axon is the critical decision-making site for cargo entry into the axon.

It may state two separate claims as one.

These results point towards an overall aggravated phenotype in the dKO mice without major effects on neuroinflammation, which is compatible with relatively normal overall development.

“Altogether, these results point towards an overall aggravated phenotype in the dKO mice without major effects on neuroinflammation, which is compatible with relatively normal overall development.”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The crystal structure of the cytosolic region covering residues 80-166 of TMEM55B has recently been solved alone and in complex with a C-terminal RILPL1 peptide.

“The crystal structure of the cytosolic region covering residues 80-166 of TMEM55B has recently been solved alone and in complex with a C-terminal RILPL1 peptide (Waschbusch et al., 2026)”

• cites Waschbusch et al., 2026Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

UNC-16 localization is concentrated at the initial segment in worms, suggesting attachment to cargo in this area.

“UNC-16 localization, which is concentrated at the initial segment in worms (Edwards et al., 2013), suggesting attachment to cargo in this area.”

• cites Edwards et al., 2013 sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

We confirmed this expression pattern by fluorescence microscopy using unc-129(2.64kb)p::GFP.

“We confirmed this expression pattern by fluorescence microscopy using unc-129(2.64kb)p::GFP (Figure 6B).”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Lysosomal positioning is critical in various cell types for the maintenance of cellular homeostasis.

“Lysosomal positioning is critical in various cell types for the maintenance of cellular homeostasis (Ballabio and Bonifacino, 2020;Bonifacino and Neefjes, 2017).”

• cites Ballabio and Bonifacino, 2020 sourceNot checked — no full text of the source
• cites Bonifacino and Neefjes, 2017 sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

Tmem55b KO has been shown to be lethal in mice.

“Interestingly, the Tmem55b KO has also been shown to be lethal in mice (Hashimoto et al., 2018).”

• cites Hashimoto et al., 2018Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

It may state two separate claims as one.

The authors' work provides robust evidence that TMEM55B has a bifunctional role in both retrograde and notably anterograde transport of lysosomes, which likely depends mostly on JIP4/UNC-16 in C. elegans.

“In summary, our work extends the knowledge of TMEM55B on lysosomal transport in vivo in highly polarized neuronal cells and provides robust evidence that TMEM55B has a bifunctional role in both retrograde and notably anterograde transport of lysosomes, which likely depends mostly on JIP4 / UNC-16 in C. elegans.”

It may state two separate claims as one.

These findings demonstrate that the mammalian TMEM55B can functionally substitute for the C. elegans Y71H2AM.2 and support the idea that the locomotor phenotype associated with Y71H2AM.2 loss originates in neurons.

“In summary, these findings demonstrate that the mammalian TMEM55B can functionally substitute for the C. elegans Y71H2AM.2 and support the idea that the locomotor phenotype associated with Y71H2AM.2 loss originates in neurons.”

It may state two separate claims as one.

TMEM55A and TMEM55B seem to play at least partially redundant functions in the mouse, although additive effects cannot be entirely excluded.

“Moreover, surprisingly, TMEM55A and TMEM55B seem to play at least partially redundant functions in the mouse, although additive effects can not be entirely excluded.”

It may state two separate claims as one.

Together, these results indicate that loss of Y71H2AM.2 disrupts the subcellular distribution of CTNS-1::mCherry-positive lysosomes in motor neurons and is accompanied by a mild impairment in locomotor activity.

“Together, these results indicate that loss of Y71H2AM.2 disrupts the subcellular distribution of CTNS-1::mCherry-positive lysosomes in motor neurons and is accompanied by a mild impairment in locomotor activity.”

It may state two separate claims as one.

The authors' data suggest a previously uncharacterized functional redundancy and a role for TMEM55A in lysosomal positioning.

“However, given the direct effect on lysosomal clustering, our data suggest a previously uncharacterized functional redundancy and a role for TMEM55A in lysosomal positioning.”

It may state two separate claims as one.

This establishes TMEM55B as a functional homolog of Y71H2AM.2 and suggests that TMEM55A and TMEM55B have in vivo properties that may differ.

“This establishes TMEM55B as a functional homolog of Y71H2AM.2 and suggests that TMEM55A and TMEM55B have in vivo properties that may differ.”

It may state two separate claims as one.

These results identify Y71H2AM.2 as a regulator of axonal lysosome motility, with a particularly prominent role in anterograde transport, and demonstrate that mammalian TMEM55B can functionally rescue these transport defects in vivo in C. elegans.

“Overall, these results identify Y71H2AM.2 as a regulator of axonal lysosome motility, with a particularly prominent role in anterograde transport, and demonstrate that mammalian TMEM55B can functionally rescue these transport defects in vivo in C. elegans.”

It may state two separate claims as one.

TMEM55B does not control the global abundance of lysosomes, but promotes their transition into a kinesin-competent transport state at the pre-axonal/AIS region.

“Our data support a hypothesis in which TMEM55B does not control the global abundance of lysosomes, but promotes their transition into a kinesin-competent transport state at the pre-axonal/AIS region.”

• AssumptionRests on an assumption: The proximal axon is the critical decision-making site for cargo entry into the axon.
• AssumptionRests on an assumption: The AIS has a great effect on the inclusion or exclusion of cargo for axon entry.

Probably not a substantial claim. The paper’s conclusions may not depend on it.

These findings do not distinguish between functional redundancy and additive, independent effects.

“These findings do not distinguish between functional redundancy and additive, independent effects”

Probably not a substantial claim. The paper’s conclusions may not depend on it.

The PAEZ regulates cargo entry to the axon by selectively regulating the attachment of motors to differentially post-translationally modified microtubules.

“The PAEZ, on the other hand, was more recently shown to regulate cargo entry to the axon by selectively regulating the attachment of motors to differentially post-translationally modified microtubules (Farias et al., 2015).”

• cites Farias et al., 2015Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.