IL-21 R (interleukin-21 receptor) is a type I transmembrane glycoprotein within the class I cytokine receptor family, type 4 subfamily (1 ‑ 5). Complex formation between IL-21 R and the common gamma  chain ( gamma _c), also used for IL-2, IL-4, IL-7, IL-9, IL-13 and IL-15 receptors, is required for signaling (6, 7). Mouse IL-21 R cDNA encodes 521 amino acid (aa) including a 19 aa signal peptide, a 218 aa extracellular domain (ECD) with 4 conserved cysteine residues, a fibronectin type III domain, and a WSXWS motif, a 21 aa transmembrane domain and a 271 aa cytoplasmic domain with a Box 1 motif, a kinase domain, and several sites for tyrosine phosphorylation (4, 5). One such site, pY510, mediates STAT binding (1, 2). The mouse IL‑21 R ECD shares 69%, 91%, 65%, 63% and 58% aa identity with human, rat, equine, canine and bovine IL-21 R, respectively. One potential 447 aa isoform, with an alternate start site at aa 83, lacks the four conserved ECD cysteines. IL-21 R 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 (1, 3 ‑ 5). Both IL‑21 and IL‑4 are necessary for efficient B cell IgG1 production and normal germinal center architecture (8). B cell IL‑21 R engagement induces Blimp-1 (which mediates plasma cell differentiation), and is important for memory responses (1, 9, 10).  IL-21 R engagement on mouse NK cells enhances their cytotoxic activity and IFN-gamma production (4, 11). IL‑21 R engagement on CD8⁺ T cells aids control of viral infection and tumor growth; IL-21 R is also necessary for sufficient numbers of regulatory T cells to combat chronic inflammation (1, 12, 13). IL‑21 R expression is often up‑regulated in allergic skin inflammation, systemic lupus erythematosus and diffuse large B cell lymphoma (DLBCL) (1, 2, 14, 15).