NXPH4 (neurexophilin 4) is a neuropeptide-like signaling molecule that functions as a critical oncogenic regulator across multiple cancer types. The protein acts as a signaling receptor ligand, binding to neurexins and modulating cellular pathways 1. In cancer biology, NXPH4 promotes malignant progression through multiple mechanisms: it stabilizes HIF1A by competitively binding PHD4, amplifying hypoxia signaling in colorectal cancer 2; regulates glycolysis and reactive oxygen species via NDUFA4L2 in bladder cancer 3; and interacts with CDKN2A to regulate cell cycle progression in non-small cell lung cancer 4. NXPH4 expression is transcriptionally controlled by ETS1 in oral squamous cell carcinoma and promotes macrophage M2 polarization 5. Clinically, elevated NXPH4 expression correlates with poor prognosis and reduced survival in colorectal cancer, bladder cancer, and hepatocellular carcinoma 267. NXPH4 is associated with immune cell infiltration and chemotherapy resistance, making it a pan-cancer prognostic biomarker 7. Additionally, serum NXPH4 serves as an early diagnostic marker for hepatocellular carcinoma 8. These findings position NXPH4 as a potential therapeutic target for cancer treatment.