Tspan8 is a member of the transmembrane 4 superfamily, also known as the tetraspanin family.

Tetraspanin 8 is expressed in squamous epithelial cells (not epidermis), capillary endothelial cells, nerves, smooth and striated muscle cells, and subpopulations of hematopoietic progenitor cells.

Like other tetraspanins, Tspan8 act as a "molecular facilitator" by forming a web in glycolipid-enriched membrane microdomains, called TEM (tetraspanin enriched membrane domains). Tspan8 associates with additional tetraspanins, integrins, preferentially CD49c, CD104, but also CD49d. It is directly associated with EWI-F, CD13 and intersectin 2. Via its associated molecules Tspan8 becomes involved in cell adhesion and motility as well as signal transduction. Motility promotion mostly proceeds via its association with CD104 and is in line with pronounced metastatic spread of Tspan8 overexpressing tumors as described for hepatocellular cancer. Similar to other tetraspanins, Tspan8 is abundantly present in exosomes, where it accounts via its association with CD49d for endothelial cell and endothelial cell progenitor targeting with the consequence of endothelial cell activation and endothelial cell progenitor maturation.
Regulates cell motility and survival and is involved in the promotion of angiogenesis.

Not known in Homo sapiens.