Two laboratories (29, 30) independently reported a new immunodeficiency due to heterozygous gain-of-function mutations in the p110δ-catalytic subunit of PI3K, which is encoded by PIK3CD. Angulo et al. (29) reported a series of 17 patients with activated PI3K-δ syndrome (APDS) due to an E1012K mutation in PIK3CD. Lymphocytes from the patients had increased levels of activated Akt and phosphatidylinositol 3, 4, 5-triphosphate (PIP3), and increased activation-induced cell death. This evidence concerns the gene PIK3CD and immunodeficiency disease.