OXSM (3-oxoacyl-ACP synthase, mitochondrial) is a mitochondrial ketosynthase that catalyzes fatty acid biosynthesis. The enzyme functions as a key component of mitochondrial fatty acid synthesis (mtFAS), capable of synthesizing both the lipoic acid precursor octanoate and longer-chain fatty acids 1. OXSM operates through transacylation and condensation reactions with mitochondrial acyl carrier protein (mACP), with detailed structural studies revealing conserved gating mechanisms that regulate substrate selectivity 1. Mechanistically, OXSM activity is regulated by post-translational modifications and protein stability. HSP60 (HSPD1) directly interacts with OXSM to maintain its protein stability; HSP60 knockdown destabilizes OXSM and reduces lipoic acid synthesis 2. Additionally, lactylated PCK2 competitively inhibits Parkin-mediated ubiquitination of OXSM, thereby modulating mtFAS and bioenergetic metabolism during hepatic ischemia-reperfusion injury 3. Clinically, OXSM dysregulation associates with multiple disease states. In oral squamous cell carcinoma, OXSM is upregulated via enhancer-driven transcriptional activation by CBFB, promoting metastatic progression and lipid synthesis 4. In ovarian cancer, OXSM downregulation promotes proliferation and migration 2. OXSM serves as a diagnostic biomarker in rheumatoid arthritis 5, bladder cancer 6, and kidney stone susceptibility 7, suggesting broader metabolic dysfunction in disease pathogenesis.