Although no functional variants of IL-21 has been identified in NOD mice, due to the critical role of IL-21 in T cell-mediated pathogenesis, IL-21 or IL-21R knockout renders NOD mice resistant to the onset of T1D.[43,44] In human, the IL-2/IL-21 locus is a common genetic factor in autoimmune diseases, including T1D, RA, and celiac diseases.[37] It is essential to determine the functional variants of both IL-2 and IL-21 that leads to the breach of immune tolerance to self-tissues. The gene discussed is IL21; the disease is type 1 diabetes mellitus.