ACSM1 catalyzes the first step of fatty acid metabolism by activating medium-chain fatty acids (C4-C10) to acyl-CoA, with particular relevance to butyric and decanoic acids 1. Beyond canonical fatty acid metabolism, ACSM1 regulates lipid composition by promoting monounsaturated fatty acid accumulation while reducing polyunsaturated fatty acid production, thereby modulating cellular ferroptosis sensitivity 2. Clinically, ACSM1 exhibits context-dependent roles across multiple diseases. In prostate cancer, androgen receptor-induced ACSM1 and ACSM3 enhance fatty acid oxidation for energy production and confer ferroptosis resistance, driving therapy resistance to AR antagonists 3. ACSM1 also promotes prostate cancer progression via interaction with 15-PGDH, modulating PGE2 signaling and extracellular matrix remodeling 4. In hepatocellular carcinoma, METTL3-mediated m6A modification of ZNF384 transcriptionally activates ACSM1, supporting tumor growth and glucose metabolism 5. Conversely, in colorectal cancer, MOGAT2-mediated suppression of ACSM1 inhibits proliferation and EMT, positioning ACSM1 as a pro-tumorigenic metabolic driver 6. Additionally, ACSM1 genetic variants associate with schizophrenia and major depressive disorder susceptibility in Han Chinese populations 7, and ACSM1 downregulation via RIPK4 activation contributes to cisplatin-induced acute kidney injury through ferroptotic mechanisms 2. Finally, miR-144-5p/ACSM1 axis modulation alleviates doxorubicin-induced cardiotoxicity by suppressing lipid peroxidation 8.