CD81, a member of the tetraspanin family, is a widely expressed cell-surface protein that plays a crucial role in various biological responses, including cell adhesion, morphology, activation, proliferation, and differentiation of B and T cells. It is part of the CD21-CD19 co-receptor complex on mature B cells, which enhances B cell activation by bridging antigen-specific recognition and CD21-mediated complement recognition. On T cells, CD81 associates with CD4 and CD8, providing a costimulatory signal with CD3. Additionally, CD81 is physically and functionally associated with several integrins, influencing cell adhesion and migration. It is also implicated in the entry of hepatitis C virus into human cells, serving as a receptor molecule that binds to the viral envelope protein E2. CD81's engagement activates signaling cascades like Raf/MEK/ERK, which affect post-entry steps of the virus life cycle. Furthermore, CD81 is expressed at high levels in normal germinal center B cells and is found in most non-Hodgkin lymphomas, suggesting its role in lymphoma pathogenesis.