TSPAN6 (tetraspanin 6) is a transmembrane scaffold protein that functions as a tumor suppressor and regulator of cellular signaling. As a member of the tetraspanin family, TSPAN6 localizes to plasma membranes and extracellular vesicles 1, where it regulates protein trafficking and membrane compartmentalization. TSPAN6 suppresses RAS-driven tumorigenesis by binding EGFR and blocking EGFR-induced RAS activation, with loss of TSPAN6 promoting epithelial-to-mesenchymal transition 2. In colorectal cancer, TSPAN6 deletion increases adenoma formation through enhanced EGF signaling via syntenin-1-mediated TGF-α trafficking 3. Conversely, TSPAN6 is upregulated in gliomas, correlating with poor prognosis and enhanced macrophage infiltration 4. TSPAN6 regulates exosome biogenesis through interaction with syntenin-1, increasing multivesicular body and intraluminal vesicle formation; TSPAN6-enriched exosomes from adipose-derived stem cells enhance wound healing 5. In the central nervous system, TSPAN6 modulates hippocampal synaptic transmission and long-term potentiation 6. Clinical significance includes TSPAN6 as a predictive marker for EGFR-targeted therapy response in colorectal cancer 3 and prognostic indicator in gliomas and pancreatic cancer 7. TSPAN6 deletions have been identified in rare genetic diseases including epilepsy and intellectual disability 8.