MECR (mitochondrial trans-2-enoyl-CoA reductase) catalyzes the NADPH-dependent reduction of trans-2-enoyl thioesters, catalyzing the final step of mitochondrial fatty acid synthesis (mtFAS) 1. The enzyme displays preference for medium-chain substrates and accepts both acyl carrier protein and CoA thioesters as substrates [UniProt]. Beyond lipid synthesis, MECR regulates iron homeostasis and ceramide metabolism, with loss of function impairing Fe-S cluster assembly and increasing ceramide levels 2. MECR is required for proper mitochondrial morphology, bioenergetic function, and neuronal maintenance 2. A cryptic cytoplasmic MECR isoform, produced through alternative splicing, has antiviral activity against influenza virus independent of mtFAS function 3. Biallelic MECR mutations cause MEPAN syndrome (Mitochondrial Enoyl CoA Reductase Protein-Associated Neurodegeneration), characterized by childhood-onset dystonia, basal ganglia abnormalities, and progressive optic atrophy with relative cognitive sparing 4. MECR mutations also cause LHON-like optic neuropathy 5. MECR is downregulated in Parkinson's disease patients, linking lipid metabolism dysfunction to neurodegeneration 6. In hepatocellular carcinoma, MECR is upregulated, and knockdown inhibits proliferation and promotes apoptosis, suggesting oncogenic function 1.