It has been demonstrated that perturbations in the expression or function of some Tyr phosphatases can lead to immunodeficiency on the one hand, when the altered phosphatase, for example CD45, is required for TCR signaling (Kung et al., 2000; Tchilian et al., 2001), or on the other hand, autoimmunity, when the altered phosphatase is a negative regulator of TCR signaling, for example, protein tyrosine phosphatase (PTP)N22 (Todd et al., 2007; Bottini and Peterson, 2014). Here, PTPN22 is linked to Autoimmunity.