ACSM3 (acyl-CoA synthetase medium chain family member 3) is a mitochondrial enzyme that catalyzes the activation of medium-chain fatty acids by CoA to produce acyl-CoA, representing the first step in fatty acid metabolism 1. The enzyme shows preference for medium-chain fatty acids, particularly dodecanoic acid (C12:0), and plays a crucial role in mitochondrial fatty acid oxidation and energy production 2. ACSM3 maintains mitochondrial homeostasis and prevents oxidative stress by facilitating proper medium-chain fatty acid metabolism 3. The enzyme functions as a tumor suppressor in multiple cancers, with downregulated expression associated with poor prognosis in hepatocellular carcinoma, breast cancer, acute myeloid leukemia, and clear cell renal cell carcinoma 4567. Loss of ACSM3 leads to metabolic dysfunction, including impaired fatty acid oxidation, mitochondrial dysfunction, and increased susceptibility to ferroptosis 1. In kidney disease, ACSM3 deficiency aggravates fibrosis through disrupted medium-chain fatty acid metabolism 2. Conversely, in prostate cancer, ACSM3 is upregulated and promotes tumor growth by enhancing fatty acid oxidation and protecting against ferroptosis 1. ACSM3 expression is regulated by various factors including HNF4α, IGF2BP2, IGF2BP3, and METTL14-mediated m6A methylation 867.