Elovl4, short for Elongation of Very Long chain fatty acids-4, is an elongase in the ELOVL family of fatty acid elongases. It is uniquely responsible for catalyzing the production of very long chain (VLC, ≥C28) saturated (VLC-SFA) and polyunsaturated (VLC-PUFA) fatty acids in tissues like the brain, retina, skin, Meibomian glands, and testes. These VLC-FA play crucial roles in maintaining cell structure and function, modulating membrane fluidity, and cell signaling. Genetically engineered mouse models have been instrumental in studying its functions [1,2,3].

Using cell culture and genetically engineered mouse models, researchers found that different mutations in Elovl4 can lead to various neurological and tissue-specific disorders in humans. Heterozygous mutations can cause autosomal dominant Stargardt-like macular dystrophy (STGD3) or spinocerebellar ataxia-34 (SCA34), while homozygous mutations result in severe seizures, ichthyosis, and other serious conditions. For example, in cell culture, specific Elovl4 mutants associated with SCA34 showed differential capabilities in VLC-PUFA and VLC-SFA biosynthesis, which may explain the lack of retinal phenotype in SCA34 and contribute to its pathogenic mechanism [1-3,6-9].

In conclusion, Elovl4 is essential for the biosynthesis of VLC-SFA and VLC-PUFA, which are crucial for neural function, retina health, and other biological processes. Studies using KO/CKO mouse models have provided insights into how Elovl4 mutations can lead to diseases such as STGD3, SCA34, and severe infantile-onset disorders, highlighting its significance in understanding the mechanisms of these diseases and potentially developing novel therapies [1-3,6-9].

References:

1. Hopiavuori, Blake R, Anderson, Robert E, Agbaga, Martin-Paul. 2018. ELOVL4: Very long-chain fatty acids serve an eclectic role in mammalian health and function. In Progress in retinal and eye research, 69, 137-158. doi:10.1016/j.preteyeres.2018.10.004. https://pubmed.ncbi.nlm.nih.gov/30982505/

2. Deák, Ferenc, Anderson, Robert E, Fessler, Jennifer L, Sherry, David M. 2019. Novel Cellular Functions of Very Long Chain-Fatty Acids: Insight From ELOVL4 Mutations. In Frontiers in cellular neuroscience, 13, 428. doi:10.3389/fncel.2019.00428. https://pubmed.ncbi.nlm.nih.gov/31616255/

3. Yeboah, Gyening Kofi, Lobanova, Ekaterina S, Brush, Richard S, Agbaga, Martin-Paul. 2021. Very long chain fatty acid-containing lipids: a decade of novel insights from the study of ELOVL4. In Journal of lipid research, 62, 100030. doi:10.1016/j.jlr.2021.100030. https://pubmed.ncbi.nlm.nih.gov/33556440/