Haploinsufficiency of shank3, arising from mutations, deletions [4,11–13], or epigenetic modifications [14] that disrupt SHANK3 protein expression or function is identified in a notable proportion (0.5–2%) of individuals with autism spectrum disorder (ASD) and is the primary cause of Phelan-McDermid syndrome (PMS, 22q13.3 deletion) [15–18]. The gene discussed is SHANK3; the disease is Phelan-McDermid syndrome.