AKR1A1 is an NADPH-dependent oxidoreductase that catalyzes reduction of diverse carbonyl-containing compounds, including aldehydes, ketones, and monosaccharides, with preference for negatively charged substrates like glucuronate 1. The enzyme functions as a detoxification enzyme, reducing toxic aldehydes including methylglyoxal and lipid-derived compounds like acrolein 2. AKR1A1 also mediates S-nitroso-CoA reduction, thereby inhibiting protein S-nitrosylation and regulating metabolic reprogramming in renal proximal tubules, particularly through inhibition of PKM2 S-nitrosylation 3. The enzyme participates in xenobiotic and drug metabolism, including anthracyclines doxorubicin and daunorubicin 4. Clinically, AKR1A1 dysregulation associates with multiple pathologies. It emerges as a molecular hub for diabetic kidney disease, with deficiency contributing to cellular dysfunction 5. In osteoporosis, lactylation-dependent AKR1A1 upregulation in monocytes and macrophages drives metabolic-immune reprogramming via SPP1-CD44 signaling 6. In gastric cancer, elevated AKR1A1 promotes glucose and lipid metabolism reprogramming, driving proliferation and chemoresistance through RORα-mediated regulation 7. Additionally, ROS-dependent AKR1A1 expression shifts mesenchymal stem cell lineage commitment toward adipogenesis, implicating it in age-related osteoporosis pathogenesis 8. Loss of AKR1A1 increases oxidative stress sensitivity in astrocytes 9, highlighting its protective role against oxidative damage.