Ovine 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 sheep (Ovis aries). 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 regulate gene expression in B cells, T cells, and natural killer (NK) cells. IL-21 promotes B cell proliferation, plasma cell differentiation, immunoglobulin class switching, and antibody production, while enhancing CD8⁺ T cell cytotoxic activity and NK cell function. In healthy sheep, basal IL-21 expression is generally low but increases during infection, vaccination, and immune activation. Ovine IL-21 has been implicated in immune responses to pathogens such as ovine lentivirus (maedi-visna), Mycobacterium avium subspecies paratuberculosis, gastrointestinal nematodes (e.g., Haemonchus contortus), and respiratory pathogens. In veterinary and agricultural research, ovine IL-21 serves as a biomarker of T cell–dependent B cell help and humoral immunity and is studied in the context of vaccine efficacy, host–pathogen interactions, and regulation of adaptive immune responses in small ruminant health and production systems.