HAGH encodes hydroxyacylglutathione hydrolase, also known as glyoxalase II, which catalyzes the final step of the glyoxalase pathway by hydrolyzing S-D-lactoyl-glutathione to form glutathione and D-lactic acid 1. The gene produces both cytosolic and mitochondrial isoforms through alternative transcription and translation initiation, with the mitochondrial form containing an N-terminal targeting sequence that directs it to the mitochondrial matrix 2. This dual localization allows HAGH to function in both compartments where methylglyoxal detoxification occurs. The enzyme plays a crucial role in cellular metabolism by recycling glutathione and producing D-lactate, which can serve as a substrate for protein lactoylation—a post-translational modification that regulates glycolytic enzymes 1. HAGH is located on chromosome 16.3 34. Clinically, elevated plasma HAGH levels are associated with Alzheimer's disease specifically in APOE ε4 carriers, suggesting involvement in oxidative stress pathways during neurodegeneration 5. Additionally, HAGH protein levels are positively correlated with hyperuricemia risk, indicating potential roles in mitochondrial dysfunction-related metabolic disorders 6. These findings highlight HAGH's importance in cellular detoxification and its emerging relevance as a biomarker for age-related diseases.