The necessity of tightly balanced regulation of PI3K activity is also illustrated in patients with activated PI3Kδ syndrome (APDS): overactive PI3Kδ signaling leads to a variable degree of humoral immunodeficiency, impaired control of EBV infection, lymphoproliferation and lymphoma and some immune dysregulation [34,35,36,37]. This evidence concerns the gene PIK3CD and activated PI3K-delta syndrome.