IL-21 R (interleukin-21 receptor) is a type I transmembrane glycoprotein that belongs to 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, and IL-15 receptors, is required for signaling (6, 7). Rat IL-21 R cDNA encodes a 521 amino acid (aa) precursor that contains a 19 aa signal peptide, a 218 aa extracellular domain (ECD) a 21 aa transmembrane domain and a 263 aa cytoplasmic domain. The ECD shows 4 conserved cysteine residues, a fibronectin type III domain, and a WSXWS motif; the cytoplasmin region possesses a Box1 motif, a kinase domain, and several sites for tyrosine phosphorylation (4, 5). One such site, pY502, mediates STAT binding (1, 2). The rat IL‑21 R ECD shares 70%, 91%, 66%, 63% and 58% aa identity with human, mouse, equine, canine and bovine IL-21 R, respectively. One potential 445 aa isoform is reported that contains an alternative start site at Met77. If expressed, it would lack three of the four conserved ECD cysteines seen in full-length rat IL-21 R (8). 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 (9). IL-21 engagement of the IL‑21 receptor on B cells induces Blimp-1 (which mediates plasma cell differentiation), and is important for memory responses (1, 10, 11). IL‑21 R engagement on mouse NK cells enhances their cytotoxic activity and IFN-gamma production (4, 12). 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, 13, 14). IL‑21 R expression is often up‑regulated in allergic skin inflammation, systemic lupus erythematosus and diffuse large B cell lymphoma (DLBCL) (1, 2, 15, 16).