Hyperactivation of the PI3K/AKT/mTOR/S6K signaling pathway in immune cells can be the consequence of heterozygous GOF mutations in the genes encoding for PI3Kδ that cause an immune dysregulation disorder called activated PI3Kδ syndrome [APDS; also known as “p110δ activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency” (PASLI)] (47). This evidence concerns the gene PIK3CA and immunodeficiency disease.