HAO2, short for hydroxyacid oxidase 2, is a flavin mononucleotide-dependent peroxisomal enzyme. It is involved in the oxidation of l-2-hydroxy acids to ketoacids, generating hydrogen peroxide. Hao2 has been associated with fatty acid metabolic processes, lipid catabolic processes, and is potentially related to blood pressure regulation as it was identified as a candidate gene for blood pressure quantitative trait locus [1,2,5,6,7].

In rats with chronic kidney disease (CKD), single-cell transcriptome sequencing showed that HAO2 expression in proximal tubular cells was significantly reduced. Overexpression of HAO2 enhanced fatty acid metabolism by promoting the fatty acid oxidation (FAO) pathway, protecting proximal tubular cells from injury [1]. In clear cell renal cell carcinoma (ccRCC), low HAO2 expression was associated with shorter survival, and overexpression of HAO2 promoted the lipid catabolic process, inhibiting the malignancy of ccRCC cells [2]. In hepatocellular carcinoma (HCC), HAO2 was underexpressed, and its overexpression inhibited HCC cell motility and tumorigenicity in nude mice [3,4,5].

In conclusion, HAO2 plays crucial roles in fatty acid and lipid metabolism-related biological processes. Research on HAO2, especially through over-expression and in vivo models like nude mice in cancer studies and rat models in kidney disease research, has revealed its potential as a protective factor in CKD and a tumor suppressor in ccRCC and HCC. Understanding HAO2's functions may provide new insights into these disease mechanisms and potential treatment strategies.