Interleukin-21 receptor (IL-21R) is a type I transmembrane glycoprotein within the class I cytokine receptor family, type 4 subfamily. Complex formation between IL-21R and the common γ chain (γc) is required for signaling. IL-21R is expressed mainly on B cells (highest on mature, activated, follicular and germinal center 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. B cell IL-21R engagement induces Blimp1 (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 upregulated in allergic skin inflammation, systemic lupus erythematosus and diffuse large B cell lymphoma (DLBCL).