ALDOB (aldolase B) is a glycolytic enzyme that catalyzes the aldol cleavage of fructose-1,6-bisphosphate into dihydroxyacetone phosphate and D-glyceraldehyde-3-phosphate during glycolysis and gluconeogenesis 1. In fructolysis, ALDOB metabolizes fructose-1-phosphate derived from dietary fructose into these same triose phosphates. Beyond its catalytic role, ALDOB functions as a molecular adapter with tumor-suppressive properties, stabilizing protein complexes that regulate glucose metabolism and cell signaling 2. Mechanistically, ALDOB interacts with multiple signaling proteins: it forms a complex with FBP1, PP2A-C, and AKT to prevent insulin hyperresponsiveness and maintain lipid homeostasis 3, and associates with AKT1 to inhibit AKT phosphorylation within the HNF4A/ALDOB/AKT1 axis 4. Post-translational modifications regulate ALDOB activity; ketogenic diet-induced lysine β-hydroxybutyrylation at Lys108 inhibits ALDOB enzymatic activity and suppresses cancer cell proliferation 5. Clinically, ALDOB downregulation associates with chemotherapy resistance in pancreatic cancer and poor prognosis in hepatocellular carcinoma 24. ALDOB deficiency in tumor cells upregulates TGF-β expression, promoting immune evasion through T cell exhaustion 6. ALDOB also appears as a biomarker in non-alcoholic fatty liver disease plasma proteomes 7, suggesting diagnostic potential in metabolic liver disease.