TSPAN31 (tetraspanin 31) is a four-transmembrane domain protein that functions as an oncogenic regulator in multiple cancer types through its role in cell proliferation, migration, and survival signaling 1. The protein promotes malignant potential by activating key oncogenic pathways, particularly the PI3K/AKT signaling cascade, which drives cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) in gastric cancer, breast cancer, and glioma 123. TSPAN31 also regulates fatty acid metabolism by modulating FASN, SREBP1, and ACSL1 expression levels 2. Uniquely, TSPAN31 serves as a natural antisense transcript to CDK4, directly suppressing CDK4 mRNA and protein expression by targeting its 3'-UTR, which affects cell cycle regulation 45. In hepatocellular carcinoma, TSPAN31 acts as a critical regulator of survival and apoptotic signals through modulation of Akt signaling components including p-GSK3β and β-catenin 5. Clinically, TSPAN31 overexpression correlates with advanced tumor stages, lymphatic invasion, and poor patient prognosis across multiple cancer types, making it both a potential prognostic biomarker and therapeutic target 13. The protein's expression is regulated by miR-135b and p53 5.