Activated phosphoinositide 3-kinase δ syndrome (APDS, also known as PASLI- p110δ-activating mutations causing senescent T cells, lymphadenopathy, and immunodeficiency) is caused by heterozygous GOF mutations in PIK3CD (APDS1/PASLI-CD) or PIK3R1 (APDS2/PASLI-R1) that induce hyperactivation of the enzyme PI3Kδ (9–12, 42). Here, PIK3R1 is linked to immunodeficiency disease.