PTPN22 and Autoimmunity: Lymphoid tyrosine phosphatase is a critical regulator of signaling through the T-cell receptor, and in T-cells, it forms a complex with the kinase Csk.8 The autoimmune-associated PTPN22 C1858T variant does not bind kinases well, and appears to encode a gain-of-function enzyme.12,26 The mechanism of action of PTPN22 in autoimmunity remains unclear.