Indeed, Shank3-dependent molecular, structural, and functional changes of excitatory synapses have been deeply characterized from in vitro and in vivo studies to elucidate some of the key underlying pathophysiological mechanisms (Han et al., 2013; Wang et al., 2016) and to provide potential therapeutic approaches for SHANK3-associated brain disorders, mainly ASDs (Bozdagi et al., 2013; Shcheglovitov et al., 2013; Duffney et al., 2015; Bidinosti et al., 2016; Vicidomini et al., 2016; Wang et al., 2016). The gene discussed is SHANK3; the disease is brain disorder.