CD63, also known as LAMP-3, is a glycoprotein belonging to the tetracaine family, primarily located in late endosomes, lysosomes, and secretory vesicles across various cell types. It is expressed intracellularly in resting platelets and basophils, but upon activation, CD63 translocate to the plasma membrane, making it a widely used marker for basophil activation. Unlike basophils, mast cells can expose CD63 without activation. CD63 is expressed on activated platelets, monocytes, macrophages, and granulocytes, as well as endothelial cells, fibroblasts, and smooth muscle cells. It interacts with integrins (such as VLA-3 and VLA-6) and TIMP-1, playing roles in mediating allergic responses, phagocytosis, and cell migration. Additionally, CD63 is involved in the regulation of H/K-ATPase trafficking and ROMK1 channels, and serves as a T-cell stimulation molecule. CD63 expression can be used to predict prognosis in early-stage carcinomas and is identical to the melanoma-associated antigen ME491 and the platelet antigen PTLGP40. Diseases associated with CD63 dysfunction include melanoma and Hermansky-Pudlak Syndrome, highlighting its significance in both immune responses and disease processes.