It has been found that abnormalities in PAD4 (Peptidyl arginine deiminase 4) structure and function lead to a significantly increased risk of developing RA, and that dysregulation of PAD4-mediated citrullination of extracellular proteins is a driver of the autoimmune response in RA, as 75% of patients develop anticitrullinated protein antibodies (ACPA) [62]. This evidence concerns the gene PADI4 and rheumatoid arthritis.