Despite the advent of highly effective targeted biologics against pro-inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-17 (IL-17) in the treatment of rheumatoid arthritis, spondylarthritis, and psoriasis, major challenges still remain, including incomplete response in some patients, recurrence upon cessation of treatment and loss of response over time1–6, providing a strong argument for the need of deeper understanding of disease mechanisms in autoimmune diseases. The gene discussed is TNF; the disease is rheumatoid arthritis.