ELOVL4 is an endoplasmic reticulum-bound fatty acid elongase that catalyzes the rate-limiting condensation reaction in the synthesis of very long-chain fatty acids (VLCFAs) with ≥28 carbons, adding two carbons per elongation cycle 1. ELOVL4 synthesizes both very long-chain saturated (VLC-SFA) and polyunsaturated (VLC-PUFA) fatty acids that serve as precursors for membrane lipids and bioactive mediators 2. In the retina, ELOVL4 produces VLC-PUFAs that are incorporated into photoreceptor outer segment membranes and converted to "elovanoid" compounds supporting photoreceptor survival 2. In the brain, VLC-SFAs are incorporated into sphingolipids enriched in synaptic vesicles, regulating neurotransmitter release kinetics 2. ELOVL4 also mediates CD4+ T cell positive selection in the thymus 3 and promotes wound healing by producing docosahexaenoic acid and eicosapentaenoic acid, which dampen pro-inflammatory cytokines 4. Mutations in ELOVL4 cause three distinct human diseases: heterozygous mutations causing C-terminal truncation lead to autosomal dominant Stargardt disease 3 (STGD3) through protein mislocalization and aggregation 5; heterozygous missense mutations cause spinocerebellar ataxia 34 (SCA34) with variable erythrokeratoderma presentation 6; and homozygous mutations cause severe infantile-onset disease with seizures, spasticity, intellectual disability, and ichthyosis 1. Staphylococcus aureus dysregulates skin barrier function by suppressing ELOVL4 expression through pro-inflammatory cytokines 7.