Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Essential for trafficking and compartmentalization of CD19 receptor on the cell surface of activated B cells. Upon initial encounter with a microbial pathogen, enables the assembly of CD19-CR2 and B cell receptor complexes at signaling TERMs, lowering the threshold dose of antigen required to trigger B cell clonal expansion and humoral immune response. In T cells, associates with CD4 or CD8 coreceptors and defines the maturation state of antigen-induced synapses with B cells. Facilitates localization of CD3 in these immune synapses, required for costimulation and sustained activation of T cells, preferentially triggering T helper type 2 immune response. Can act both as positive and negative regulator of homotypic or heterotypic cell-cell fusion processes. In myoblasts, associates with another tetraspanin CD9 in complex with PTGFRN and inhibits myotube fusion during muscle regeneration. In macrophages, associates with CD9 and beta-1 and beta-2 integrins, and prevents macrophage fusion into multinucleated giant cells specialized in ingesting complement-opsonized large particles. Also prevents the fusion between mononuclear cell progenitors into osteoclasts in charge of bone resorption. Positively regulates sperm-egg fusion and may be involved in the acrosome reaction. Regulates protein trafficking in intracellular compartments. In T cells, associates with dNTPase SAMHD1 and defines its subcellular location, enabling its degradation by the proteasome and thereby controlling intracellular dNTP levels. Also regulates integrin-dependent migration of macrophages, particularly relevant for inflammatory response in the lung.; (Microbial infection) Specifically required for Plasmodium yoelii infectivity of hepatocytes, controlling sporozoite entry in hepatocytes via the parasitophorous vacuole and subsequent parasite differentiation to exoerythrocytic forms.