Tetraspanins comprise a large superfamily of cell surface-associated membrane proteins with four transmembrane domains. On cell membranes, tetraspanins form networks of various proteins called tetraspanin-enriched microdomains (TEMs). CD63 was the first characterized tetraspanin and it is found in TEMs, as well as late endosomes and lysosomes. In late endosomes, CD63 is enriched on the intraluminal vesicles, and can be secreted as exosomes through fusion of endosomes with the plasma membrane. The complex localization pattern of CD63 suggests that its intracellular trafficking and distribution must be tightly regulated. CD63 contains N-link glycosylation sites that produce diverse CD63 molecules that range from 30 to 60 kDa depending on cell type. CD63 is an important exosomal marker in cancer cells, and may be involved in cancer progression and metastasis.
