Of the non-HLA genes, the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene located on chromosome 1p13 has the strongest association with T1D.65PTPN22 codes for a lymphoid-specific phosphatase that is expressed in lymphocytes and is an inhibitor of T cell activation.65 Substitution of arginine for tryptophan at position 620 disrupts binding between PTPN22 and the intracellular kinase, Csk, altering responsiveness of T and B cells to receptor stimulation.66 This leads to decreased inhibition of T cell activation, and promotes multiorgan autoimmunity. Here, PTPN22 is linked to type 1 diabetes mellitus.