Following the initial description in 2013 of gain-of-function (GOF) mutations resulting in enhanced phosphoinositide 3-kinase (PI3K) δ signaling as the cause of a combined immune deficiency syndrome [the activated phosphoinositide 3-kinase δ syndrome (APDS), also known as p110δ-activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency (PASLI)], multiple case reports and several case series have highlighted the protean clinical feature of this newly recognized disease. This evidence concerns the gene PIK3CD and immunodeficiency disease.