While present in almost all categories, their burden and distribution vary, with certain defects acting as clear ‘hotspots’, such as IPEX syndrome, APECED, LRBA, RAG1, RAG2, CD3γ, Helios, ARPC1B, and CD55 deficiencies. The gene discussed is AIRE; the disease is immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome.