ACOX3 (acyl-CoA oxidase 3, pristanoyl) is a peroxisomal enzyme that catalyzes the first step of fatty acid β-oxidation, specifically oxidizing CoA-esters of 2-methyl-branched fatty acids 1. The enzyme localizes to both peroxisomal matrix and cytosol, where it functions in peroxisomal fatty acid metabolism alongside other acyl-CoA oxidases (ACOX1 and ACOX2) 2. ACOX3 plays a critical role in maintaining vascular smooth muscle tone, as demonstrated by functional studies showing that ACOX3 dysfunction leads to loss of basal myogenic tone in arterial smooth muscle cells and hypersensitivity to sympathomimetic stimuli 3. The enzyme shows differential expression patterns across various cancer types, with upregulation in some cancers and downregulation in others, suggesting context-dependent roles in tumorigenesis 4. ACOX3 expression is modulated by metabolic regulators like Sirt1, particularly in cardiac lipid metabolism, where its downregulation contributes to improved cardiac function in diabetic cardiomyopathy 1. Clinical studies have identified ACOX3 as a potential therapeutic target for post-traumatic stress disorder and various cancers 56. The enzyme's activity is sensitive to pharmacological interventions, with compounds like nintedanib and atorvastatin affecting its expression in cancer and metabolic contexts 78.