CD63 (melanoma-associated antigen, ME491) is a tetraspanin and a member of the transmembrane 4 superfamily. It is a cell surface-associated protein characterized by four transmembrane domains. As a tetraspanin, CD63 forms networks with a variety of proteins, called tetraspanin-enriched microdomains (TEMs). It is localized in different membranes of the cell, including the cell membrane and membranes of lysosomes and granules, including the platelet dense granules and the Weibel-Palade bodies of endothelial cells. The complex localization pattern suggests a tightly regulated trafficking and distribution process. CD63 is often used as a platelet activation marker, as cell surface expression increases due to platelet granule secretion after platelet activation.

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