CASK

CASK is a calcium/calmodulin-dependent serine/threonine kinase that belongs to the membrane-associated guanylate kinase scaffold family, combining an N-terminal catalytic domain with PDZ, SH3, and guanylate kinase-like interaction modules. Unlike classical CaMKs, its activity is largely calcium-independent. CASK localizes to synaptic and epithelial junctions, binding neurexins, neuroligins, syndecans, and the transcription factor Tbr-1, and it phosphorylates neurexin and other junctional substrates. It participates in synaptogenesis, neuronal migration, and transcriptional regulation of cortical development. Human mutations in CASK cause X-linked intellectual disability, microcephaly with pontocerebellar hypoplasia, and FG syndrome, underscoring its essential role in brain development.