ACAA1 (acetyl-CoA acyltransferase 1) is a peroxisomal enzyme that catalyzes the thiolytic cleavage of straight-chain 3-oxoacyl-CoAs, playing a crucial role in fatty acid β-oxidation 1. The enzyme processes short, medium, long, and very long-chain fatty acids in peroxisomes, contributing to cellular energy metabolism 1. Mechanistically, ACAA1 supplies acyl-carnitines to mitochondria for fatty acid oxidation and maintains ATP production, with knockout reducing oxygen consumption by 60% and ATP production by 70% in cancer cells 2. ACAA1 also interacts with cell cycle regulators, specifically CDK4, influencing RB1 phosphorylation and G1-S transition 3. Disease relevance includes significant dysregulation in multiple cancers, where it often shows tissue-specific expression patterns - downregulated in lung and head/neck cancers but upregulated in breast and endometrial cancers 1435. In Alzheimer's disease, the N392S mutation represents a monogenic risk factor, and ACAA1 depletion blocks biosynthesis of long-chain polyunsaturated fatty acids including docosahexaenoic acid 6. Clinically, ACAA1 serves as a prognostic biomarker across various malignancies and represents a potential therapeutic target, with compounds like trimetazidine showing efficacy in reducing ACAA1 levels 34.