GRHPR encodes glyoxylate and hydroxypyruvate reductase, a cytoplasmic and peroxisomal enzyme that catalyzes the reduction of glyoxylate to glycolate and hydroxypyruvate to D-glycerate, using NADH or NADPH as cofactors 1. The enzyme has higher affinity for NADPH (Km 0.011 mM) compared to NADH (Km 2.42 mM) and demonstrates a Km of 1.0 mM for glyoxylate reduction 1. GRHPR plays a protective role in glyoxylate metabolism by converting glyoxylate to the less reactive glycolate, preventing oxalate accumulation 1. Loss-of-function mutations in GRHPR cause Primary Hyperoxaluria Type 2 (PH2), an autosomal recessive disorder characterized by oxalate overproduction and deposition in kidneys and other organs 23. Multiple pathogenic mutations have been identified, including missense mutations (G165D, R302C), nonsense mutations, and deletions, with mutant proteins showing severely reduced enzymatic activity (1.5-5.6% of wild-type) 34. PH2 represents approximately 20% of primary hyperoxaluria cases and is significantly underdiagnosed, with genetic testing revealing a prevalence of about 1:58,000 25. Beyond metabolic function, GRHPR acts as a tumor suppressor in hepatocellular carcinoma, with its expression regulated by miR-138-5p 6.