In this “Perspectives” article, we review and comment on current advances in Shank3 research and include some original data that show common Shank3 deficits in a number of seemingly unrelated human neurological disorders that include sporadic Alzheimer’s disease (AD), autism spectrum disorder (ASD), bipolar disorder (BD), Phelan–McDermid syndrome (PMS; 22q13.3 deletion syndrome), and schizophrenia (SZ). The gene discussed is SHANK3; the disease is Alzheimer disease.