ACOX1 (acyl-CoA oxidase 1) encodes the first and rate-limiting enzyme of the very-long-chain fatty acid (VLCFA) β-oxidation pathway in peroxisomes 1. This enzyme catalyzes VLCFA oxidation and produces hydrogen peroxide as a byproduct 1. ACOX1 plays crucial roles in lipid metabolism and energy homeostasis, with hepatic expression increasing in obesity contexts 2. The enzyme functions primarily in peroxisomal fatty acid β-oxidation, contributing to cellular energy production and lipid catabolism 3. ACOX1 regulates systemic metabolism through inter-organ communication - liver-specific knockout protects mice from diet-induced obesity and insulin resistance by modulating circulating ω-3 VLCFAs that promote adipose tissue browning via GPR120 activation 2. The protein is essential for neuronal health, as both loss-of-function and gain-of-function mutations cause axonal loss through distinct mechanisms - deficiency leads to developmental defects while overactive variants (p.N237S) increase reactive oxygen species production 1. ACOX1 dysfunction is implicated in non-alcoholic fatty liver disease (NAFLD), where PFAS exposure upregulates ACOX1, leading to oxidative stress and hepatic lipid accumulation 4. Additionally, ACOX1 has emerged as a potential therapeutic target in colorectal cancer, where it contributes to nucleotide metabolism pathways affecting tumor progression 5.