Elongation of very long chain fatty acids protein 4 (ELOVL4) (ELOVL4)

Elongation of very long chain fatty acids protein 4 (ELOVL4) is a critical enzyme localized in the endoplasmic reticulum that facilitates the synthesis of very-long-chain fatty acids (VLCFAs) and ultra-long-chain fatty acids (ULCFAs) exceeding 26 carbons in length (UniProt Q9GZR5). It is highly expressed in specialized tissues including the retina, brain, skin, and testes, where these specific lipids are essential for structural integrity and signaling (NCBI Gene 6785). In the retina, ELOVL4 is responsible for producing VLC-polyunsaturated fatty acids (VLC-PUFAs) that are vital for photoreceptor cell survival and function. Mutations in the ELOVL4 gene are primary causes of autosomal dominant Stargardt macular dystrophy 3 (STGD3) and spinocerebellar ataxia type 34 (SCA34) (OMIM 605512). Furthermore, ELOVL4 is indispensable for the formation of the skin's permeability barrier; its deficiency leads to fatal neonatal skin dehydration in animal models (PubMed PMID: 15310750). Although there are currently no FDA-approved drugs that directly target ELOVL4, it is an active area of research for gene replacement therapies and lipid-based nutritional interventions aimed at restoring VLCFA levels in affected tissues (PubMed PMID: 30265446). The enzyme's role in maintaining the blood-retina and blood-brain barriers makes it a significant focus for understanding neurodegenerative and ocular pathologies. Future therapeutic strategies may involve small molecule modulators to enhance enzyme activity or bypass the metabolic block caused by pathogenic mutations.

Other names

3-keto acyl-CoA synthase ELOVL4ELOVL fatty acid elongase 4STGD2SCA34ADMD

Catalyzes the condensation of fatty acyl-CoA with malonyl-CoA, which is the first and rate-limiting step in the four-step fatty acid elongation cycle in the endoplasmic reticulum.