GNPAT (glyceronephosphate O-acyltransferase) is a peroxisomal enzyme that catalyzes the first committed step in plasmalogen biosynthesis by acylating dihydroxyacetone phosphate 1. Plasmalogens are ether lipids with a distinctive vinyl ether linkage at the sn-1 position of the glycerol backbone, conferring unique biophysical properties essential for cell signaling and membrane function 2. Beyond canonical plasmalogen synthesis, GNPAT participates in broader metabolic regulation. Post-translational acetylation of GNPAT by ACAT1 at lysine 128 stabilizes the lipogenic enzyme FASN by preventing TRIM21-mediated degradation, promoting hepatic lipid metabolism and hepatocarcinogenesis 3. Peroxisome-derived plasmalogens regulate mitochondrial dynamics in adipose tissue; GNPAT knockdown impairs cold-induced mitochondrial fission and thermogenesis, effects rescued by plasmalogen supplementation 4. In lung tissue, GNPAT stabilizes the mitochondrial fission protein DRP1 through USP30-mediated interactions, contributing to mitochondrial dysfunction and cell apoptosis in COPD 5. Clinically, GNPAT mutations cause rhizomelic chondrodysplasia punctata 2 and developmental ocular defects 2. Genetic variants associate with post-stroke neurological instability through putative excitotoxicity pathways 6, while GNPAT does not directly regulate systemic iron homeostasis 7. Expression modulation via structural variants influences high-altitude adaptation in Tibetan cattle 8.