Mutations in the SHANK/ProSAP family genes (SHANK1–3), particularly SHANK2 and SHANK3, have been identified recently as pathogenic for non-syndromic ASDs (Durand et al., 2007; Berkel et al., 2010; Sato et al., 2012). In addition, loss of one copy of SHANK3 in Phelan-McDermid syndrome is thought to contribute to the neurobehavioral features of the disorder, including ASD (Bonaglia et al., 2001; Wilson et al., 2003). The Shank proteins function as scaffolds that organize postsynaptic densities (PSDs) in glutamatergic synapses and link receptors to cytoskeletal signaling molecules (Sheng and Kim 2000). Shank proteins have also been implicated in spinogenesis and synapse development. In particular, transfection of Shank3 is sufficient to induce dendritic spine formation in otherwise aspiny neurons (Roussignol et al., 2005). Another study provides evidence that Shank2 and Shank3 are involved in spine formation, whereas Shank1 is involved in synapse maturation and stability (Grabrucker et al., 2011).
