The tetraspanins are integral membrane proteins expressed on cell surface and granular membranes of hematopoietic cells and are components of multi-molecular complexes with specific integrins. The tetraspanin CD63 is a lysosomal membrane glycoprotein that translocates to the plasma membrane after platelet activation. CD63 is expressed on activated platelets, monocytes and macrophages, and is weakly expressed on granulocytes, T cell and B cells. It is located on the basophilic granule membranes and on the plasma membranes of lymphocytes and granulocytes. CD63 is a member of the TM4 superfamily of leukocyte glycoproteins that includes CD9, CD37 and CD53, which contain four transmembrane regions. CD63 may play a role in phagocytic and intracellular lysosome-phagosome fusion events. CD63 deficiency is associated with Hermansky-Pudlak syndrome and is strongly expressed during the early stages of melanoma progression.