P2RX4 encodes an ATP-gated nonselective cation channel permeable to potassium, sodium, and calcium ions 1. The channel plays critical roles in both normal physiology and pathological conditions. In cancer biology, P2RX4 promotes tumor progression through multiple mechanisms. Upon chemotherapy-induced cell death, dying cancer cells release ATP that activates P2RX4, triggering an mTOR-dependent pro-survival program in neighboring cells and creating therapeutic vulnerabilities 1. P2RX4 overexpression is associated with poor prognosis across multiple cancer types and promotes malignant behaviors including cell proliferation, invasion, and resistance to apoptosis 23. The receptor facilitates hepatocellular carcinoma progression by increasing intracellular calcium levels and activating PI3K/AKT signaling pathways 3. In non-cancer contexts, P2RX4 contributes to autophagy regulation and lysosomal function 45. The channel also participates in immune system modulation, influencing macrophage and T regulatory cell infiltration in tumors 3, and mediates fibroblast-myeloid cell crosstalk in pulmonary fibrosis through ATP-IL-6 signaling 6. Additionally, P2RX4 plays roles in vascular pathology by promoting smooth muscle cell phenotypic switching in abdominal aortic aneurysms 7.