Canine IL-21 (Interleukin-21) is a cytokine of the common γ chain (γc) family that plays a central role in regulating adaptive immune responses in dogs (Canis lupus familiaris). IL-21 is produced primarily by activated CD4⁺ T cells, particularly T follicular helper (Tfh) cells and Th17 cells, following antigen stimulation. It signals through the IL-21 receptor (IL-21R) in association with the common γ chain, activating downstream JAK/STAT pathways—predominantly STAT3—to modulate gene expression in target immune cells. IL-21 promotes B cell proliferation, plasma cell differentiation, immunoglobulin class switching, and antibody production, while also enhancing CD8⁺ T cell cytotoxicity and natural killer (NK) cell function. In healthy dogs, basal IL-21 expression is generally low but increases during infection, vaccination, and immune activation. Dysregulated IL-21 responses have been associated with chronic inflammatory and immune-mediated diseases such as atopic dermatitis, inflammatory bowel disease, immune-mediated hemolytic anemia, and autoimmune thyroiditis, as well as in certain lymphomas. Dogs serve as important translational animal models for human lymphoma, autoimmune disease, and allergic disorders. In veterinary and comparative medicine research, canine IL-21 is studied as a biomarker of T cell–dependent B cell help and humoral immune responses and as a potential target in immunotherapy and vaccine development.