ALDOC (aldolase C) is a glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate into triose phosphates, playing a central role in glycolysis and gluconeogenesis 1. Beyond its classical metabolic function, ALDOC serves as a critical regulator of cancer metabolism and immune microenvironment. Mechanistically, ALDOC functions through multiple pathways: it binds to ADP-dependent glucokinase to activate AMPK phosphorylation in prostate cancer 1, interacts with HIF1A to enhance PGK1 transcriptional activity in colorectal cancer 2, and cooperates with ENO2 to drive lactate production in 3D tumor spheroids 3. ALDOC expression is enhanced through HSP90/HIF1A stabilization in cholangiocarcinoma 4 and can be crotonylated by GCDH-mediated modifications, affecting its enzymatic activity in hepatocellular carcinoma 5. Clinically, ALDOC is significantly upregulated in multiple cancer types including colorectal, gastric, prostate, and glioblastoma, correlating with poor prognosis and advanced disease stages 26. In gastric cancer, ALDOC regulates macrophage differentiation and immune infiltration 6. In glioblastoma, ALDOC loss promotes invasion through altered serotonin metabolism and PPAR-γ signaling, with PPAR-γ agonists enhancing temozolomide sensitivity 7. ALDOC knockdown suppresses proliferation, induces apoptosis, and inhibits tumor growth across multiple cancer models, establishing it as a promising therapeutic target.