ELOVL

ELOVL, short for elongation of very long-chain fatty acids, refers to a family of enzymes localized to the endoplasmic reticulum that catalyze the first and rate-limiting step in the biosynthesis of very long-chain fatty acids (VLCFAs). In humans, the ELOVL gene family consists of seven members, ELOVL1 through ELOVL7, each with unique substrate preferences and tissue distribution.

These enzymes elongate long-chain acyl-CoA substrates by two carbon units, using malonyl-CoA as an extender, within a conserved four-step cycle that also involves dehydratation and reductive steps carried out by partner enzymes. The different ELOVLs act on distinct chain lengths and degrees of unsaturation, contributing to the diversity of VLCFAs found in sphingolipids, glycerophospholipids, and other lipid classes that populate membranes and specialized lipids such as skin barrier lipids and myelin.

Biological roles: VLCFAs are essential for skin barrier formation, myelin structure, and retina function, among other tissues. Some family members are particularly important in specific tissues; for example, ELOVL4 supplies very long-chain fatty acids critical for retinal lipids, and ELOVL1 contributes to cutaneous and neural lipids.

Clinical relevance: Mutations or dysregulation of ELOVL genes have been linked to human diseases, including neurodevelopmental and sensory disorders and skin conditions. Notably, mutations in ELOVL4 cause Stargardt-like macular dystrophy and spinocerebellar ataxia type 34 (SCAR34). Ongoing research aims to define the precise substrate specificities of each ELOVL and their roles in health and disease.