Interleukin-21 receptor (IL-21R) is a type I transmembrane glycoprotein within the class I cytokine receptor family, type 4 subfamily. IL-21R is expressed mainly on B cells, NK cells, and activated T cells, but is also found on dendritic cells, alternatively activated macrophages, intestinal lamina propria fibroblasts and epithelial cells, and keratinocytes. Both IL-21 and IL-4 are necessary for efficient B cell IgG1 production and normal germinal center architecture. B cell IL-21 R engagement induces Blimp-1(which mediates plasma cell differentiation), and is important for memory responses. IL-21R engagement on mouse NK cells enhances their cytotoxic activity and IFN-γ production. IL-21R engagement on CD8+ T cells aids control of viral infection and tumor growth? IL-21R is also necessary for sufficient numbers of regulatory T cells to combat chronic inflammation. IL-21R expression is often up-regulated in allergic skin inflammation, systemic lupus erythematosus and diffuse large B cell lymphoma (DLBCL).