Shank3 overexpression promotes the formation of new synapses and dendritic spines and regulates their shape and size (Sala et al., 2001; Roussignol et al., 2005; Grabrucker et al., 2011; Verpelli et al., 2011; Arons et al., 2012; Durand et al., 2012), whereas Shank3 knockdown or autism-associated Shank3 mutations specifically impair glutamate signaling at synapses (Verpelli et al., 2011; Arons et al., 2012). The gene discussed is SHANK3; the disease is autism.