TSPAN1 (tetraspanin 1) functions as a structural component of tetraspanin-enriched microdomains that facilitate receptor clustering and cell signaling 12. Beyond its canonical roles in cell adhesion and protein trafficking, TSPAN1 has emerged as a key regulator in multiple cancer types. Mechanistically, TSPAN1 promotes autophagy maturation through direct LC3 binding via conserved LIR motifs 3 and regulates tumor cell metabolism through the ERK-c-Myc-glycolysis axis 4. In pancreatic cancer, TSPAN1 is upregulated via the WNT-CTNNB1 signaling pathway and targeted by miR-454, forming a regulatory axis that drives proliferation 3. TSPAN1 knockdown suppresses pancreatic cancer cell migration, invasion, and survival 1, and similarly inhibits squamous cell carcinoma proliferation and motility 5. Clinically, TSPAN1 expression correlates with poor overall survival in pancreatic cancer patients 3. Recent proteomics studies identify TSPAN1 as a top-ranked plasma biomarker for prostate cancer risk prediction, with elevated levels detectable 9 years before diagnosis and predictive AUC of 0.760 for 5-year risk 6. In endometrial cancer, TSPAN1 inhibition promotes ferroptosis and reduces glycolytic metabolism 7. Additionally, TSPAN1+ B cells are significantly elevated in autoimmune hepatitis and promote disease progression through enhanced cytokine secretion and antigen presentation 8.