CD63

CD63, also known as lysosome-associated membrane glycoprotein 3 (LAMP-3), is a member of the tetraspanin family of transmembrane proteins. It is encoded by the CD63 gene in humans and is widely expressed across cell types.

Structure and features: CD63 belongs to the tetraspanin superfamily, characterized by four transmembrane helices, two extracellular loops (including a large extracellular loop), and short cytoplasmic N- and C-termini. The large extracellular loop is heavily N-glycosylated and mediates specific protein–protein interactions within tetraspanin-enriched microdomains.

Localization and trafficking: CD63 localizes primarily to late endosomes and lysosomes and is associated with lysosome-related organelles. It is also present at the plasma membrane in certain cells, particularly upon activation, and is enriched in extracellular vesicles such as exosomes.

Function: As a component of tetraspanin-enriched microdomains, CD63 participates in organizing protein interactions that influence vesicular trafficking, membrane fusion, adhesion, and signaling. It interacts with a variety of partners, including integrins and other tetraspanins, and can impact immune signaling and platelet degranulation in a context-dependent manner. Its presence on exosomes suggests roles in intercellular communication.

Clinical and research relevance: CD63 is widely used as a marker for exosomes and other extracellular vesicles and is commonly detected by antibodies in research and diagnostic contexts. Its expression and localization are studied across cancers and immune-related conditions, where it can reflect vesicular trafficking states or cellular activation, though its exact role varies by cell type and disease context.