Spontaneous mutations in the human IL-2RA (CD25) gene (13) or genetic ablation of the mouse il2ra locus result in Treg deficiency (7, 12), uncontrolled T cell expansion (14), and overt autoimmunity (13, 15), a clinical picture similar to the immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome in which Foxp3 (16), the signature transcription factor of Treg cells, is dysfunctional (17, 18). The gene discussed is IL2RA; the disease is Autoimmunity.