Calcium/calmodulin-dependent serine protein kinase and mental retardation

Ann Neurol. 2009 Oct;66(4):438-43. doi: 10.1002/ana.21755.


Calcium/calmodulin-dependent serine protein kinase (CASK) belongs to the membrane-associated guanylate kinase protein family. The members of this protein family function as multiple domain adaptor proteins originally identified at cell junctions and synapses. Insertional mutations or targeted disruption of the CASK gene in mice results in neonatal lethality, indicating an important role for CASK in development. Recently, several reports have also indicated that mutations in the human CASK gene result in X-linked malformations of the brain and mental retardation. At the molecular level, many studies indicate that CASK is critical for synapse formation at both presynaptic and postsynaptic junctions, and in the regulation of gene expression. The known molecular functions of CASK explain, at least partially, mental retardation and brain developmental defects in patients. In this review, recent findings about CASK are summarized and discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain / enzymology*
  • Brain / growth & development
  • Brain / pathology
  • Calcium-Calmodulin-Dependent Protein Kinases / chemistry
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics*
  • Disease Models, Animal
  • Humans
  • Intellectual Disability / enzymology*
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Mice
  • Mutation
  • Neurons / enzymology
  • Neurons / pathology


  • Calcium-Calmodulin-Dependent Protein Kinases