AKR1B1 (aldo-keto reductase family 1 member B1) is a NADPH-dependent cytosolic enzyme that catalyzes the reduction of diverse carbonyl-containing compounds to alcohols 1. As a key enzyme in the polyol pathway, AKR1B1 converts glucose to sorbitol during hyperglycemia and reduces endogenous metabolites including aromatic and aliphatic aldehydes, ketones, monosaccharides, bile acids, steroids, and prostaglandins. It also detoxifies dietary and lipid-derived unsaturated carbonyls such as 4-hydroxynonenal and crotonaldehyde 1. Beyond its classical metabolic roles, AKR1B1 has emerged as a critical regulator in cancer biology. In leukemia, elevated AKR1B1 expression promotes leukemogenesis by reprogramming fructose metabolism and is associated with poor prognosis 2. AKR1B1-dependent fructose production via the polyol pathway enhances cancer cell proliferation, migration, and glycolysis across multiple cancer types 3. In lung cancer, AKR1B1 drives EGFR-TKI resistance by activating STAT3 to upregulate cystine uptake and glutathione synthesis, with AKR1B1 inhibition restoring drug sensitivity 4. Similarly, in hepatocellular carcinoma, AKR1B1 inhibition with epalrestat overcomes multidrug resistance 5. AKR1B1 serves as a potential therapeutic target in diabetic kidney disease 6 and represents a candidate biomarker for cancer prognosis and treatment response.