All mammalian cell membranes are characterized by amphipathic lipid molecules that interact with proteins to confer structural and functional properties on the cell. The predominant lipid species are phospholipids, glycolipids, sphingolipids and cholesterol. These lipids contain fatty acids with variable hydrocarbon chain lengths between C14-C40, either saturated or unsaturated, that are derived from diet, synthesized de novo, or elongated from shorter chain fatty acids by fatty acid elongase enzymes. One member of the family of elongases, ELOngation of Very Long chain fatty acids-4 (ELOVL4), mediates the biosynthesis of both saturated and unsaturated very long chain fatty acids (VLC-FA; > C26) in the retina, meibomian gland, brain, skin, and testis. Different mutations in ELOVL4 cause tissue-specific maculopathy and/or neuro-ichthyotic disorders. The goal of this mini-review is to highlight how different mutations in ELOVL4 can cause variable phenotypic disorder, and propose a possible mechanism, based on the role of fatty acids in membranes, which could explain the different phenotypes.
Keywords: Autosomal dominant Stargardt-like macular dystrophy; Elongation of very long chain fatty acids-4 (ELOVL4); Erythrokeratodermia (EKV); Retinal degeneration; Spinocerebellar ataxia (SCA); Very long chain polyunsaturated fatty acids (VLC-PUFA).