The delta variant of p110, p100δ (PIK3CD), which is restricted to the leukocyte lineage, governs several aspects of immunity, and gain-of-function mutations of PIK3CD at residue E1020K have been described previously to cause activated PI3K-δ syndrome (APDS) characterized with recurrent respiratory infections, viremia, lymphadenopathy, and nodular lymphoid hyperplasia. Here, PIK3CD is linked to activated PI3K-delta syndrome.