Shank family proteins (shank1, shank2 and shank3) are neuronal scaffold proteins that organize a cytoskeleton-associated signaling complex at the postsynaptic density (PSD) of nearly all excitatory glutamatergic synapses in the mammalian brain¹.

The Shank family, including Shank1, has five conserved protein domains: 1. ankyrin repeat domain (ANK), 2. Src homology 3 (SH3) domain, 3. PSD-95/Discs large/ZO-1 (PDZ) domain, 4. proline-rich region containing homer and cortactin-binding sites (Pro), 5. sterile α motif (SAM) domain². All these domains can act as sites for specific protein-protein interactions, and the presence of these multiple domains within a single polypeptide is consistent with a function as a scaffolding protein. Shanks interact directly or indirectly with all major types of glutamate receptors: NMDA receptors, AMPA receptors, and mGluRs via different domains. Shank proteins also interact with several actin regulatory proteins and L-type Ca²⁺ (Ca_V1.3) channels in medium spiny neurons of the striatum³.

Shank1 mRNA, being synthesized in dendritic spine, can locally control the spine morphology. The Shank1 gene is located on chromosome 19q13.33 and contains 23 exons and two alternative promoters leading to two distinct isoforms⁴. Shank1 is highly expressed in the cortex and hippocampus⁵.

Recent studies indicate that Shank1 is a causative gene for idiopathic autism spectrum disorders (ASD)¹. In addition it was found that Shank1 has a role in working memory deficits in schizophrenia⁶. Shank1 knock-out mice display increased anxiety and decreased vocal communication⁷.