The MAGUK (membrane-associated guanylate kinase homologs) family of proteins contain multiple protein-binding domains and are involved in cell junction organization, tumor suppression, and signaling. CASK (also designated LIN-2) belongs to a MAGUK subfamily which is characterized by a novel domain structure that consists of a calcium/calmodulin- dependent protein kinase domain followed by PDZ, SH3 and guanylate kinase-like (GUK) domains. CASK is expressed in rat brain where it binds to cell-surface proteins, such as neurexin and syndecan, and is thought to be involved in signaling at neuronal synapses. CASK translocates to the nucleus and interacts with Tbr-1 to form a complex, which binds to a specific DNA sequence (the T-element), and induces the expression of specific genes, including Reelin. CASK displays a transcription regulation function, which appears crucial for cerebrocortical development.