CD81, also known as TAPA-1 and Tetraspanin-28, belongs to the transmembrane 4 superfamily, also known as the tetraspanin family. Members of this family mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. CD81 is a widely expressed cell-surface protein involved in an astonishing variety of biologic responses. CD81 associates with a wide range of membrane proteins including CD151, TfR2, LDL R, PCSK9, Glypican 3, IFITM1, IGSF8/CD316, FPRP, and complexes of CD19-CD21. It is related to adhesion, morphology, activation, proliferation, and differentiation of B, T, and other cells. CD81 additionally functions as a receptor for the E2 glycoprotein of hepatitis C virus. The CD81-E2 interaction inhibits NK cell cytolytic activity, provides a co-stimulatory signal to T cells, and inhibits the maturation of plasmacytoid dendritic cells.