HAO1 encodes hydroxyacid oxidase 1 (glycolate oxidase), a peroxisomal enzyme with broad substrate specificity that preferentially oxidizes glycolate to glyoxylate 12. The glyoxylate product is subsequently utilized by alanine-glyoxylate aminotransferase for peroxisomal glycine synthesis, representing a critical detoxification pathway for glyoxylate that prevents its accumulation and conversion to oxalate, which causes kidney stone formation 23. HAO1 can also catalyze oxidation of glyoxylate and long-chain hydroxyacids at lower efficiency, using molecular oxygen as the physiological electron acceptor and generating hydrogen peroxide 14. HAO1 silencing is therapeutically significant for primary hyperoxaluria type 1 (PH1), a severe metabolic disorder caused by AGXT mutations. Lumasiran, an siRNA targeting HAO1, reduces glycolate oxidase expression and urinary oxalate levels, with sustained efficacy and acceptable tolerability in clinical trials 56. CRISPR-based approaches targeting HAO1 also demonstrate efficacy and safety in preclinical PH1 models 78. A healthy woman with complete HAO1 knockout showed elevated glycolate without clinical phenotype, de-risking therapeutic HAO1 inhibition 9. Additionally, HAO1 variants associate with aortic stenosis risk independent of coronary artery disease 10, and HAO1 protein expression associates with chr20 kidney disease progression in type 2 diabetes subtypes 11.