ELOVL fatty acid elongase 4 (ELOVL4)

ELOVL fatty acid elongase 4 (ELOVL4) is a multi-pass transmembrane enzyme localized to the endoplasmic reticulum, essential for the biosynthesis of very long-chain saturated and polyunsaturated fatty acids (VLC-SFA and VLC-PUFA) with carbon chain lengths of 28 or more. ELOVL4 functions by catalyzing the first, rate-limiting step of fatty acid chain extension, a condensation reaction utilizing fatty acyl-CoA and malonyl-CoA substrates. Its activity is crucial for maintaining appropriate lipid content in photoreceptors of the retina, neurons of the central nervous system, skin, testes, and Meibomian glands. Distinct inherited mutations in the ELOVL4 gene can cause several severe monogenic diseases, including dominant Stargardt-like macular dystrophy (STGD3), spinocerebellar ataxia 34 (SCA34), and, in the homozygous state, syndromic encephalopathy with seizures and skin symptoms. ELOVL4 is not known to elongate shorter chain polyunsaturated fatty acids to docosahexaenoic acid (DHA). In the brain, its main VLC-SFA products are 28:0 and 30:0. The precise modulation or targeting of ELOVL4 remains experimentally challenging, as altering its function may have significant implications for membrane structure and cellular signaling, with notable safety concerns for the CNS and retina. There is no evidence of approved drugs that directly modulate ELOVL4, though its disease associations and biological essentiality make it a molecule of major biomedical interest.

Other names

ELOVL4Elongation of very long chain fatty acids protein 4ELOV4

Substrate mimicry or inhibition/activation of fatty acid elongation (theoretical; not established for any marketed drugs)