Cluster of Differentiation 9 (CD9), also known as Tetrapanin-29, TSPAN29 and Leukocyte Antigen MIC3, is a member of the tetraspanin superfamily, a group of proteins characterized by four transmembrane domains, two extracellular loops, and N- and C- termini cytoplasmic tails.¹

The tetraspanins family members function as organizers of the cell surface by recruiting specific partner proteins into tetraspanin-enriched microdomains. Thus, depending on the recruited protein, they influence many cellular activities in different cells, including intracellular signaling, proliferation, activation, survival, migration, invasion, adhesion, and diapedesis.¹

CD9 was originally identified as a lymphohematopoietic marker, and is indeed expressed in all the major subsets of leukocytes, however, it is also widely expressed across different cell populations including endothelial cells, neurons, glia and oocytes.^2,3

CD9 plays various roles in the immune system, it has been implicated in T cell activation and participating in the formation of immunological synapses by interacting with the integrin LFA-1 (on the T-cell side) and their ligand, the integrin ICAM-1 on the antigen presenting cell (APC) surface.^2,3 In B cells, CD9 plays a role in B cell activation and regulation of antibody production, and in mast cells is involved in the regulation of signalling pathways that influence the release of allergic mediators in response to allergens.^2,3

CD9 has complex roles in the central nervous system (CNS). It has been implicated in neurite outgrowth and cell migration in association with the neural adhesion molecule L1 (L1CAM). It is also involved in myelination and the maintaining of the myelin sheath, as well as the regulation of neural progenitor cells.⁴

Finally, CD9 is often associated with exosomes, small extracellular vesicles released by cells that play a crucial role in intercellular communication by carrying proteins, lipids, and nucleic acids between cells. CD9 is considered a marker for exosomes and detection of CD9 on the surface of extracellular vesicles is often used as a method to isolate and identify exosomes from biological fluids or cell culture supernatants.^5,6