Two JAK inhibitors are approved for patients with RA (Tofacitinib and Baricitinib) and both demonstrate efficacy as defined by improvements in DAS28-CRP scores (59–62); however, these therapies influence multiple cytokine signaling pathways, increasing the importance of understanding the impact of alterations in the IL21/IL-21R signaling pathway on disease development and progression. The gene discussed is IL21; the disease is rheumatoid arthritis.