ENO1 (enolase 1) is a multifunctional glycolytic enzyme with critical roles in cancer progression and metabolic diseases. As a canonical glycolytic enzyme, ENO1 catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate and promotes the Warburg effect in tumors 1. Beyond its glycolytic function, ENO1 acts as a moonlighting protein with diverse cellular roles 2. As an RNA-binding protein, ENO1 promotes YAP1 translation by binding cytosine-uracil-guanine-rich elements in YAP1 mRNA, activating arachidonic acid metabolism and prostaglandin E2 accumulation to drive hepatocellular carcinoma progression 3. ENO1 suppresses ferroptosis by degrading IRP1 mRNA, preventing mitochondrial iron-induced cell death in cancer cells 4. When surface-localized, ENO1 acts as a plasminogen receptor promoting tumor invasion and metastasis 1. In non-malignant contexts, ENO1 contributes to pathology through the PI3K-Akt-mTOR axis; endothelial ENO1 inhibition alleviates hypoxic pulmonary hypertension by restoring endothelial and mitochondrial function 5. In rheumatoid arthritis, ENO1 suppresses ferroptosis via the ENO1-ACO1 axis, promoting fibroblast-like synoviocyte proliferation 6. ENO1 overexpression correlates with poor prognosis across multiple tumor types 1, making it a promising biomarker and therapeutic target, with potential benefit from aspirin in liver cancer patients 3.