Individuals with progranulin haploinsufficiency exhibit features of neuronal ceroid lipofuscinosis
Open accessAbstract
Individuals with heterozygous GRN mutations exhibit clinicopathological hallmarks of neuronal ceroid lipofuscinosis.
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Lipofuscin is a key pathology in neuronal ceroid lipofuscinosis and GRN-linked frontotemporal dementia.
“While lipofuscin is key pathology in neuronal ceroid lipofuscinosis and GRN-linked frontotemporal dementia”
From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [68]
Mutations in ATP6AP2 cause X-linked adult-onset Parkinsonism or fulminant postnatal neurodegeneration.
“Mutations in ATP6AP2, which endodes another vATPase subunit, cause an X-linked adult-onset Parkinsonism or fulminant postnatal neurodegeneration.157,158”
From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [157]
The Introduction and Discussion address GRN mutations and progranulin-related neurodegeneration, not ATP6AP2. Searches for ATP6AP2, the vATPase subunit, X-linked adult-onset Parkinsonism, and postnatal neurodegeneration found no passage in our copy addressing the claim. (LLM, conf=0.76)
Experimental — accuracy not yet measuredGRN mutations likely affect lysosomal function in a disease-promoting manner.
“GRN mutations likely affect lysosomal function in a disease‐promoting manner.”
From New developments of biofluid‐based biomarkers for routine diagnosis and disease trajectories in frontotemporal dementia (2022) · cites this paper as [47]
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“7c,d, online resource), as well as those for genes associated with risks for other neurodegenerative disorders (LRRK2, SNCA and GPNMB, associated with Parkinson’s disease [8], and GRN, associated with ceroid lipofuscinosis [71] and frontotemporal dementia [4]).”
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- Authors
- Ward, M. E., Chen, R., Huang, H.-Y., Ludwig, C., Telpoukhovskaia, M., Taubes, A., Boudin, H., Minami, S. S., Reichert, M., Albrecht, P., Gelfand, J. M., Cruz-Herranz, A., Cordano, C., Alavi, M. V., Leslie, S., Seeley, W. W., Miller, B. L., Bigio, E., Mesulam, M.-M., Bogyo, M. S., Mackenzie, I. R., Staropoli, J. F., Cotman, S. L., Huang, E. J., Gan, L., & Green, A. J.
- Affiliations
- National Institutes of Health (US)
- Gladstone Institutes (US)
- University of California, San Francisco (US)
- Department of Pathology, University of California, San Francisco, San Francisco, CA 94158, USA.
- Heinrich Heine University Düsseldorf (DE)
- Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
- Northwestern University (US)
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
- Stanford Medicine (US)
- University of British Columbia (CA)
- Harvard University (US)
- San Francisco VA Medical Center (US)
- Corresponding author
- Gan, Li
- Green, Ari J.
- ORCID
- Ward, Michael E.
- Chen, Robert
- Huang, Hsin-Yi
- Ludwig, Connor
- Telpoukhovskaia, Maria
- Taubes, Ali
- Minami, Sakura S.
- Reichert, Meredith
- Albrecht, Philipp
- Gelfand, Jeffrey M.
- Cruz-Herranz, Andres
- Cordano, Christian
- Alavi, Marcel V.
- Leslie, Shannon
- Seeley, William W.
- Miller, Bruce L.
- Bigio, Eileen
- Bogyo, Matthew S.
- Mackenzie, Ian R.
- Cotman, Susan L.
- Huang, Eric J.
- Gan, Li
- Green, Ari J.
- Venue
- Science Translational Medicine
- Published
- 2017-04-12
- Volume
- 9
- Issue
- 385
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC5526610
- OpenAlex
- W2606944807
- Cited by
- 193
- References
- 30
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 17 · 2023: 17 · 2022: 25 · 2021: 33 · 2020: 28 · 2019: 22 · 2018: 16 · 2017: 9
- FWCI
- 15.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- HAL (submittedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- Funders
- National Institutes of Health (award280941)
- Topics
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
- Keywords
- progranulin, haploinsufficiency, neuronal ceroid lipofuscinosis, GRN mutations, heterozygous mutation, clinicopathological features, neurodegeneration
- MeSH terms
- Progranulins, Animals, Cells, Cultured, Frontal Lobe, Heterozygote, Humans, Lysosomes, Microscopy, Electron, Mutation, Neuronal Ceroid-Lipofuscinoses, Retina, Intercellular Signaling Peptides and Proteins, Mice, Frontotemporal Dementia, Haploinsufficiency
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