ACOX2 (acyl-CoA oxidase 2) is a peroxisomal enzyme that catalyzes the first step of fatty acid β-oxidation and oxidizes bile acid intermediates, particularly di- and tri-hydroxycholestanoic acids 1. It processes very-long chain and 2-methyl branched fatty acids for mitochondrial metabolism 2. Mechanistically, ACOX2 functions through multiple pathways: it destabilizes the MRN complex by inhibiting MRE11-RAD50 binding, activating the cGAS-STING immune pathway 3; it undergoes transcriptional regulation by TEF in response to celastrol 4; and its translation is modulated by the KRT14-eIF4H interaction 5. ACOX2 operates through the PPARα pathway in hepatocellular carcinoma 6. Clinically, ACOX2 deficiency causes congenital bile acid synthesis defect 6, characterized by C27-bile acid accumulation and hypertransaminasemia responsive to ursodeoxycholic acid treatment 7. In cancer contexts, reduced ACOX2 expression associates with poor prognosis across renal cell carcinoma, endometriosis-related ovarian neoplasms, and lung cancer 3, 8, 2. Elevated ACOX2 expression predicts sensitivity to PARP inhibitors combined with immunotherapy in renal cancer 3 and ferroptosis induction 4. ACOX2 also contributes to cisplatin resistance when downregulated in bladder cancer 5.