PIK3CD and activated PI3K-delta syndrome: The first published cases of APDS were described concurrently by two different groups [38,39], showing that mutations of the PIK3CD gene, encoding the catalytic p110δ subunit of the PI3Kδ enzyme, resulted in elevated lipid kinase activity of PI3Kδ and led to hyperactivation of PIP3-AKT-mTOR-S6K signaling (Figure 2B).