Fatty acyl-CoA reductase 1 (FAR1)

Fatty acyl-CoA reductase 1 (FAR1) is an enzyme localized primarily to the peroxisomal membrane, with the ability to localize to lipid droplets under conditions of increased triglyceride synthesis. FAR1 catalyzes the NADPH-dependent reduction of long-chain fatty acyl-CoA (mainly C16–C18) to fatty alcohols, which are essential precursors for the biosynthesis of ether lipids (including plasmalogens) and wax monoesters. Its catalytic activity and subcellular targeting are critical for normal lipid metabolism. FAR1 plays a crucial role in human health, as loss-of-function mutations are associated with severe neurodevelopmental disorders, intellectual disability, congenital cataracts, and other syndromic features; the enzyme's activity is also finely regulated by plasmalogen levels through feedback mechanisms. FAR1 belongs to the short chain dehydrogenase/reductase (SDR) superfamily and is sometimes termed male sterility domain-containing protein 2 due to homology with related proteins. There is currently no record of approved drugs targeting FAR1 directly, but it is considered a key enzymatic therapeutic target for disorders of ether lipid metabolism.

Other names

Fatty acyl-CoA reductase 1FAR1MLSTD2UNQ2423/PRO4981FLJ22728SDR10E1Male sterility domain-containing protein 2short chain dehydrogenase/reductase family 10E member 1CSPSDPFCRD

Enzymatic reduction of long-chain fatty acyl-CoA to fatty alcohols using NADPH as a cofactor