Rheumatoid arthritis (RA) is thought to develop through “multiple hits”,[1] with genetic and environmental risk factors,[2] followed by antibodies such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA),[3–5] that accumulate during an “at-risk” pre-clinical phase. The gene discussed is PRTN3; the disease is rheumatoid arthritis.