RA remains a prototypic inflammatory autoimmune disease with a poorly understood etiopathogenesis despite recent advances in unraveling the genetic contribution to RA revealing over 50–60 risk loci.28, 29, 30, 31 RA is very heterogeneous as highlighted by a stronger genetic contribution to anti-citrullinated protein antibodies (ACPA)-positive disease compared with ACPA-negative disease, potentially resulting in two divergent pathogenic models32, 33, 34 with different rates of progression35, 36, 37 and response to treatment.36, 38. The gene discussed is PRTN3; the disease is rheumatoid arthritis.