In affected joints of RA, [Ca2+]ex also determines the activity of the extracellular Ca2+-dependent enzyme peptidylarginine deiminase 4 (PAD-4)56, which citrullinates proteins in the joint and thereby triggers an autoimmune response in the form of anti-citrullinated protein antibody (ACPA) production. The gene discussed is PRTN3; the disease is rheumatoid arthritis.