DHDH (dihydrodiol dehydrogenase) is a metabolic enzyme with NAD(P)+-dependent oxidoreductase activity involved in carbohydrate metabolism. It catalyzes the reduction of 1,5-anhydro-D-fructose to 1,5-anhydro-D-glucitol with exceptional catalytic efficiency (kcat/KM = 1208 s⁻¹mM⁻¹), making it the most efficient primate anhydrofructose reductase identified 1. DHDH also exhibits D-xylose dehydrogenase activity and participates in multiple carbohydrate catabolic pathways. In cancer biology, DHDH plays a critical immunoregulatory role. In triple-negative breast cancer (TNBC), DHDH-mediated D-xylose metabolism drives immune evasion by suppressing proteasome subunit PSMB9 and reducing CD8+ T cell activation, creating "cold tumors" resistant to immunotherapy 2. D-xylose supplementation reverses this phenotype, enhancing T cell cytotoxicity and checkpoint blockade sensitivity. DHDH was identified as a prognostic gene in hepatocellular carcinoma within an immune-metabolic signature predicting poor overall survival 3. Genetic variation in DHDH is associated with disease susceptibility. DHDH variants (rs2270941, rs11666105) show increased prevalence in familial Dupuytren's disease 4, and altered DHDH expression correlates with both Dupuytren's disease and alcohol-related digestive malignancies 5. Additionally, DHDH expression changes associate with behavioral domestication traits in mammals 6.