ACSM2A (acyl-CoA synthetase medium chain family member 2A) catalyzes the activation of medium-chain fatty acids (C4-C10) and xenobiotics like benzoate by conjugating them to CoA, producing acyl-CoA—the essential first step in fatty acid metabolism 1. This two-step enzymatic process involves initial CoA-ligase activation followed by glycine conjugation for detoxification 2. Structurally, ACSM2A undergoes substantial domain rearrangement driven by ligand identity, with key residues including Lys557 and a conserved Arg-Glu salt bridge facilitating catalysis 3. ACSM2A is predominantly expressed in liver mitochondrial matrix and specifically in renal proximal tubular cells, where expression correlates with tubule maturation and function 4. Clinically, ACSM2A expression decreases in acute and chr16 kidney injury, suggesting utility as a novel biomarker for proximal tubular dysfunction 4. Additionally, ACSM2A is associated with metabolic health and inflammation regulation; genome-wide studies identified it among genes correlating with estimated glomerular filtration rate 5, and multiomics analysis linked ACSM2A to carotid plaque pathogenesis 6. While ACSM2A polymorphisms elevate transaminase levels, they show limited direct impact on valproic acid-induced hepatotoxicity 7. The gene remains highly conserved evolutionarily, emphasizing its essential role in metabolic homeostasis 2.