However, it was not until the early 2000s that the genetic defect, localized in the centromeric region of the X chromosome (Xp11.23-Xq13.3) was identified [71] and closed the pathophysiological loop between the clinical presentation of IPEX disease, the crucial role of FoxP3 signaling and regulatory T cells functions [4, 6, 76]. Here, FOXP3 is linked to immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome.