P2RY2 is a G protein-coupled purinergic receptor that binds ATP and UTP with equal affinity, activating phospholipase C-mediated calcium signaling pathways 1. The receptor is widely distributed throughout human tissues, including the gastrointestinal tract where it plays important roles in epithelial barrier function and ion transport, particularly chloride flux regulation in airway epithelia 12. P2RY2 demonstrates significant clinical relevance in cancer progression, where it promotes tumor growth through activation of AKT/GSK-3β/VEGF and PI3K/AKT-mTOR signaling pathways 34. In gastric cancer, P2RY2 activation enhances cell proliferation, migration, and epithelial-mesenchymal transition markers 3. Similarly, in pancreatic ductal adenocarcinoma, P2RY2 promotes glycolytic metabolism and tumor growth through crosstalk with PDGFR signaling, leading to upregulation of c-Myc and HIF1α 4. The receptor also contributes to esophageal squamous cell carcinoma progression via circRNA-mediated mRNA stabilization 5. Interestingly, naturally occurring antibodies against P2RY2 are decreased in Alzheimer's disease patients, suggesting potential involvement in neurodegeneration 6. These findings position P2RY2 as both a potential therapeutic target for cancer treatment and a biomarker for various diseases.