While disorders resulting in overactivation of the PI3K pathway are the most researched, disorders resulting from homozygous variants in PIK3CD [30–32], PIK3CG (encoding p110γ) [33, 34], PIK3R1 [45, 46], and LCP2 (encoding Src2 homology domain 2-containing leukocyte protein of 76kDa or SLP76) [51] have been shown to result in reduced activity of this critical immune pathway, again leading to immunodeficiency and immune dysregulation. This evidence concerns the gene PIK3CD and immunodeficiency disease.