Impairment of both Treg and Teff functions underlies the onset of IPEX and patients present with many different autoimmune manifestations, such as type 1 diabetes, life-threatening enteropathy, eczema, and cytopenia.35 For the development of a lifelong FOXP3 gene therapy using HSPCs, it is necessary to achieve constitutive expression of FOXP3 in the Treg compartment without having FOXP3 overexpression perturb the proliferation and function of HSPCs or Teff cells. This evidence concerns the gene FOXP3 and immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome.