The shifts seen in this equilibrium could be the result of direct mutations in FOXP3 such as in IPEX syndrome, other polymorphisms that affect Treg function or stability, or could occur due to the influence of the surrounding tissue environment, since normal cellular mechanisms of differentiation and function that work to maintain the Treg : Teff balance are often dysregulated during autoimmunity (Figure 1). The gene discussed is FOXP3; the disease is immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome.