IL21 is a pleiotropic cytokine that orchestrates adaptive immune responses through multiple mechanisms. Functionally, IL21 promotes T follicular helper (Tfh) cell differentiation and germinal center formation, critical for effective antibody responses 1. It induces IgG production in B cells and, in synergy with IL15 and IL18, stimulates interferon-gamma production in T and NK cells 2. IL21 also reprograms differentiated effector CD8+ T cells into central memory-like cells with enhanced persistence, a property exploited therapeutically in adoptive cell therapy 3. Mechanistically, IL21 signals through the IL-21 receptor and common gamma chain, activating STAT and PI3K pathways 1. Its pleiotropy presents clinical challenges: while enhancing CAR-T and TCR-T cell function against solid tumors 4, IL21 also drives autoreactive B cell expansion and plasma cell differentiation in systemic lupus erythematosus 5. Genetically, IL21 polymorphisms associate with celiac disease susceptibility 6 and sepsis risk 7, though not with type 1 diabetes in Japanese populations 8. Clinically, IL21-based therapies show promise in cancer immunotherapy but require structural optimization to modulate autoimmune manifestations 1.