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Cited by 69Fatty Acid Research and HealthLipid metabolism and biosynthesisSphingolipid Metabolism and Signaling

Very long chain fatty acid-containing lipids: A decade of novel insights from the study of ELOVL4.

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Yeboah, Gyening Kofi, Lobanova, Ekaterina S., Brush, Richard S., Agbaga, Martin-Paul·2021·Journal of Lipid Research
DOI 10.1016/j.jlr.2021.100030PMC PMC8042400
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Abstract

Lipids play essential roles in maintaining cell structure and function by modulating membrane fluidity and cell signaling. The fatty acid elongase-4 (ELOVL4) protein, expressed in retina, brain, Meibomian glands, skin, testes and sperm, is an essential enzyme that mediates tissue-specific biosynthesis of both VLC-PUFA and VLC-saturated fatty acids (VLC-SFA). These fatty acids play critical roles in maintaining retina and brain function, neuroprotection, skin permeability barrier maintenance, and sperm function, among other important cellular processes. Mutations in ELOVL4 that affect biosynthesis of these fatty acids cause several distinct tissue-specific human disorders that include blindness, age-related cerebellar atrophy and ataxia, skin disorders, early-childhood seizures, mental retardation, and mortality, which underscores the essential roles of ELOVL4 products for life. However, the mechanisms by which one tissue makes VLC-PUFA and another makes VLC-SFA, and how these fatty acids exert their important functional roles in each tissue, remain unknown. This review summarizes research over that last decade that has contributed to our current understanding of the role of ELOVL4 and its products in cellular function. In the retina, VLC-PUFA and their bioactive "Elovanoids" are essential for retinal function. In the brain, VLC-SFA are enriched in synaptic vesicles and mediate neuronal signaling by determining the rate of neurotransmitter release essential for normal neuronal function. These findings point to ELOVL4 and its products as being essential for life. Therefore, mutations and/or age-related epigenetic modifications of fatty acid biosynthetic gene activity that affect VLC-SFA and VLC-PUFA biosynthesis contribute to age-related dysfunction of ELOVL4-expressing tissues.

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  • VLC-PUFAs are especially important for the normal function of the retina and cerebellum.

    “These are especially important for the normal function of the retina and cerebellum (Yeboah et al., 2021), which may account for the more pronounced pathologies observed in these tissues in RDLKD.”

    From The neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models (2025) · cites this paper as Yeboah et al., 2021

    The section on retinal function says VLC-PUFAs are essential for the overall health and function of the retina and RPE. The section on tissue-specific disorders does not establish the same role in the cerebellum: it says VLC-PUFAs have not been detected in normal brain, while leaving open the possibility that they are rapidly used there. Thus the retinal part is supported, but the cerebellar part is not. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • ELOVL4 is selectively expressed in the skin, testis, and nervous system.

    “ELOVL4 is selectively expressed in the skin, testis, and nervous system (Yeboah et al., 2021), and its activity, along with that of CNS-specific desaturases, may partly explain the predominantly neurological phenotype in ACBD5-deficient mice and humans.”

    From The neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models (2025) · cites this paper as Yeboah et al., 2021

    The tissue-distribution section lists skin, testes, and brain among ELOVL4-expressing tissues. It also lists the retina and Meibomian glands, so the citing sentence's selective-expression description omits sites identified by the source. No page number is provided in the supplied passage. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Retina and cerebellum exhibit the highest expression levels of ELOVL4, the elongase responsible for synthesizing VLCFAs.

    “Notably, these two tissues exhibit the highest expression levels of ELOVL4, the elongase responsible for synthesizing VLCFAs (Yeboah et al., 2021; Sherry et al., 2017).”

    From The neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models (2025) · cites this paper as Yeboah et al., 2021

    The section on ELOVL4 tissue distribution (page unavailable) says ELOVL4 synthesizes very-long-chain fatty acids and is expressed in the retina and brain. It identifies the sites of highest expression within the eye, but does not say that the retina and cerebellum have the highest expression levels among tissues. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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Authors
Yeboah, G. K., Lobanova, E. S., Brush, R. S., & Agbaga, M.-P.
Affiliations
  • University of Florida (US)
  • Dean McGee Eye Institute (US)
Corresponding author
Agbaga, Martin-Paul
ORCID
Venue
Journal of Lipid Research
Publisher
Elsevier BV
Published
2021
Volume
62
Pages
100030
ISSN
0022-2275 (ISSN-L)
DOI
10.1016/j.jlr.2021.100030
PMC
PMC8042400
OpenAlex
W3126193042
Cited by
69
References
11
Citations by year
2026: 6 · 2025: 19 · 2024: 10 · 2023: 19 · 2022: 10 · 2021: 5
FWCI
1.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Lipid Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Oklahoma Center for the Advancement of Science and Technology
  • National Institutes of Health (R01 EY030513, R21 AR076035)
  • Knights Templar Eye Foundation (EY030043, P30EY021725, R01EY04149, R21NS090117)
  • Presbyterian Health Foundation
  • Research to Prevent Blindness
  • BrightFocus Foundation
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
Keywords
ELOVL4, very long chain fatty acids, very long chain polyunsaturated fatty acids, very long-chain saturated fatty acids, fatty acid elongation, retina, brain, synaptic vesicles, neurotransmitter release, neuroprotection, skin barrier, sperm function, epigenetic regulation
MeSH terms
Acetyltransferases, Animals, Eye Proteins, Fatty Acids, Humans, Membrane Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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