Class IA PI3Ks, of specific interest in the context of vascular malformations are heterodimers consisting of catalytic subunits (p110α, p110β, and p110δ, encoded by PIK3CA, PIK3CB, and PIK3CD, respectively) in complex with a p85-type regulatory subunit (of which there are five isoforms, encoded by PIK3R1, PIK3R2, and PIK3R3) (Fig. 1) [20]. The gene discussed is PIK3R1; the disease is vascular malformation.