HAO2 is a peroxisomal flavin mononucleotide-dependent oxidase that catalyzes the oxidation of medium and long-chain hydroxyacids, such as 2-hydroxyhexadecanoate and 2-hydroxyoctanoate, to corresponding 2-oxoacids 1. This enzyme plays a critical role in fatty acid alpha-oxidation, utilizing oxygen as the physiological electron acceptor and producing hydrogen peroxide 1. HAO2 demonstrates substrate specificity, remaining inactive on glycolate, glyoxylate, L-lactate, and 2-hydroxybutanoate 1. Clinically, HAO2 functions as a tumor suppressor. Expression is significantly downregulated across multiple cancer types including hepatocellular carcinoma (HCC), where low HAO2 levels correlate with poor survival, increased metastasis, and higher tumor grade 23. In clear cell renal cell carcinoma (ccRCC), HAO2 inhibits malignancy by promoting lipid catabolic processes and suppressing lipid accumulation, with HAO2 included in fatty acid metabolism-related prognostic signatures 45. HAO2 expression is negatively regulated by miR-615-5p in HCC 3. Additionally, HAO2 variants have been associated with salt-sensitive hypertension through renal oxidative stress mechanisms 6, and HAO2 loci show associations with hydroxyurea response in sickle cell disease 7. Reintroduction of HAO2 in tumor cells impairs tumorigenesis, establishing it as a valuable diagnostic, prognostic, and potential therapeutic target.