SHANK proteins are scaffolding adaptors that have been shown to integrate neurotransmitter receptors into the cortical cytoskeleton at postsynaptic densities. SHANK1-3 of the SHANK/ProSAP family are molecular scaffolds in the postsynaptic density (PSD). SHANK recruits betaPIX and PAK to dendritic spines to regulate postsynaptic structure and interacts with ionotropic receptor and metabotropic glutamate receptor complexes. Transcript splice variation in the Shank family influences the spectrum of Shank-interacting proteins in the PSDs of adult and developing brain to ensure normal development.