HOGA1 encodes 4-hydroxy-2-oxoglutarate aldolase 1, a mitochondrial matrix enzyme that catalyzes the final step in hydroxyproline catabolism, a key pathway in glyoxylate metabolism 1. The enzyme converts 4-hydroxy-2-oxoglutarate into glyoxylate and pyruvate, preventing toxic oxalate accumulation 1. Pathogenic variants in HOGA1 cause primary hyperoxaluria type III (PH3), an autosomal recessive disorder characterized by excessive urinary oxalate excretion and nephrolithiasis 2. PH3 comprises approximately 10% of primary hyperoxaluria cases 2. Most identified variants are missense mutations resulting in loss of enzymatic function through protein misfolding defects 21. Notably, HOGA1 variants demonstrate ethnic-specific founder effects, particularly in Caucasian (c.700+5G>T) and Ashkenazi Jewish populations 3. Clinically, PH3 typically presents with urolithiasis in early childhood, with median symptom onset around 18 months 4. Compared to PH1 and PH2, PH3 demonstrates slower renal function decline but earliest symptom appearance 5. However, recent evidence indicates PH3 is more severe than previously recognized, with 8% of patients developing end-stage renal disease 2. Beyond its primary role in oxalate metabolism, HOGA1 loss-of-function promotes pancreatic ductal adenocarcinoma growth via LARP7-CDK1 pathway activation 6.