Blocking TNF signaling through its receptors TNFR1 and TNFR2 has been widely targeted in clinical trials of autoimmune and inflammatory diseases, such as rheumatoid arthritis, Crohn’s disease, ankylosing spondylitis, psoriasis, and psoriatic arthritis. The gene discussed is TNFRSF1A; the disease is ankylosing spondylitis.