HAO2 is a peroxisomal oxidase that catalyzes the oxidation of medium and long chain 2-hydroxyacids to their corresponding 2-oxoacids, with a probable role in fatty acid alpha-oxidation. The enzyme uses oxygen as its physiological electron acceptor, producing hydrogen peroxide. HAO2 expression is consistently downregulated across multiple cancer types and preneoplastic lesions, establishing it as a tumor suppressor. In hepatocellular carcinoma, HAO2 downregulation occurs early in development and inversely correlates with grading, metastatic ability, and survival; reintroduction of HAO2 in rat HCC cells impairs tumorigenicity 1. In clear cell renal cell carcinoma, low HAO2 associates with shorter overall and disease-free survival, and HAO2 overexpression inhibits lipid accumulation and suppresses KRAS signaling and cell proliferation 2. HAO2 expression is regulated post-transcriptionally by miR-615-5p and miR-1293 in hepatocellular and renal carcinomas, respectively 34. Recent evidence indicates HAO2 also influences blood pressure regulation; in salt-sensitive hypertension models, upregulated renal HAO2 increases oxidative stress through a GRK4–TPI1–histone acetylation pathway 5. HAO2 has been incorporated into prognostic gene signatures for predicting survival outcomes in ccRCC and identified as a candidate locus influencing hydroxyurea response in sickle cell disease 67. These findings position HAO2 as a metabolic tumor suppressor with potential utility as a diagnostic marker and therapeutic target.