ACADM encodes medium-chain acyl-CoA dehydrogenase (MCAD), a mitochondrial enzyme that catalyzes the first step of fatty acid beta-oxidation by dehydrogenating medium-chain fatty acyl-CoA substrates (C6-C12) 1. The enzyme requires flavin adenine dinucleotide (FAD) incorporation and assembles into functional tetramers within mitochondria 1. MCAD transfers electrons to electron-transferring flavoprotein (ETF), which subsequently feeds into the mitochondrial respiratory chain for energy production 1. Deficiency in ACADM causes medium-chain acyl-CoA dehydrogenase deficiency (MCADD), a fatty acid oxidation disorder commonly detected through newborn screening 2. Clinical diagnosis relies on elevated octanoylcarnitine (C8) in plasma and hexanoylglycine excretion in urine 2. Over 54 genetic variants have been identified, with many classified as variants of unknown significance requiring biochemical correlation for clinical interpretation 2. The enzyme shows altered expression in various pathological conditions including acute myocardial infarction, where it exhibits increased expression in cardiomyocytes, fibroblasts, and macrophages 3. ACADM has also been implicated in colorectal cancer liver metastasis through regulation of ferroptosis-related proteins 4, and inflammatory bowel disease pathogenesis 5.