GLO1 (glyoxalase I) is a cytosolic enzyme that catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione, serving as the primary detoxification enzyme for the reactive dicarbonyl methylglyoxal (MG) 1. This metabolic function prevents accumulation of MG and subsequent formation of advanced glycation end-products (AGEs) that damage proteins and DNA 2. GLO1 expression is regulated by NAD+-dependent mechanisms involving SIRT2 and NAMPT in skeletal muscle, with reduced GLO1 levels observed in obesity preceding type 2 diabetes development 3. Clinically, GLO1 amplification occurs in 8.4% of human cancers, particularly breast (22%), sarcomas (17%), and lung cancers (11.3%), where it promotes cell proliferation and survival through cell cycle pathway activation 45. GLO1 overexpression in hepatocellular carcinoma correlates with poor prognosis and enhanced cell proliferation and migration 5. Conversely, GLO1 inhibition reduces angiogenesis and tumor vascular density in triple-negative breast cancer 6. GLO1 also provides protective effects against microvascular complications in diabetes and supports vascular homeostasis 7. Additionally, GLO1 modulates TNF-induced NF-κB transcriptional activity and is required for normal osteoclastogenesis, indicating broader roles in immune and bone metabolism.