ACSM2B (acyl-CoA synthetase medium chain family member 2B) catalyzes the first step in fatty acid metabolism by activating medium-chain fatty acids (C4-C10) to acyl-CoA intermediates 12. Located in the mitochondrial matrix, ACSM2B also metabolizes xenobiotics including benzoate (found in food preservatives) and salicylate (aspirin metabolite) through a two-step glycine conjugation pathway 34. The enzyme is the predominant ACSM transcript in human liver, with expression levels sixfold higher than other ACSM family members 5. ACSM2B is highly conserved across populations, suggesting its essential role in maintaining CoA and glycine homeostasis 3. Genome-wide association studies identified ACSM2B variants associated with serum metabolite levels in African Americans 6 and gout susceptibility in Japanese populations 7. Clinical significance includes ACSM2B's upregulation during cardiac ischemia/reperfusion injury recovery 8, and evidence that rare variants may impair benzoate detoxification capacity 9. The enzyme represents the second-most abundant ACS isoform in liver after ACSL1 10. However, kinetic characterization and effects of genetic variants on enzyme activity remain poorly understood.