ALDOA encodes aldolase A, a glycolytic enzyme catalyzing the reversible conversion of fructose 1,6-bisphosphate into two triose phosphates, playing a key role in both glycolysis and gluconeogenesis 1. Beyond its canonical enzymatic function, ALDOA serves as a scaffolding protein involved in various cellular processes including insulin secretion regulation and cytoskeletal organization 1. Mechanistically, ALDOA activity is regulated through post-translational modifications. Lactylation at specific lysine residues (K147, K230/322) inhibits enzymatic activity but triggers gain-of-function effects including enhanced protein stability, nuclear translocation, and altered protein-protein interactions 234. Transcriptional regulation occurs through multiple pathways: NR4A3 directly binds ALDOA promoter regions to enhance glycolytic activity 5, while POU2F1 similarly upregulates ALDOA expression to promote metabolic reprogramming 6. ALDOA also participates in non-canonical signaling, functioning as an effector in MRGPRE-β-arrestin-1-mediated metabolic signaling 7. Clinically, ALDOA dysregulation associates with hepatocellular carcinoma, where CTNNB1 mutation-driven ALDOA phosphorylation promotes glycolysis and proliferation 8, and with liver cancer stem cells where lactylation maintains stemness 4. ALDOA mutations cause glycogen storage disease 12, representing its primary genetic disease association. Enhanced ALDOA activity promotes oxaliplatin resistance in colon cancer through metabolic reprogramming 6, identifying it as a potential therapeutic target.