CASK is a multidomain scaffolding protein kinase located on the X chromosome X plays critical roles in synaptic development and neural function 1. As a component of the presynaptic cytomatrix at the active zone, CASK organizes synaptic vesicle release machinery through extensive interactions with CAZ proteins 2. The protein functions as a molecular hub binding cell-surface adhesion molecules including neurexins, syndecans, and amyloid precursor protein, linking extracellular signaling to intracellular cytoskeletal organization 1. CASK regulates synaptic plasticity and memory formation by controlling CaMKII autophosphorylation, with studies in Drosophila demonstrating that CASK function in mushroom body neurons is necessary and sufficient for memory consolidation 3. In developing human cortical neurons, CASK is essential for establishing functional synaptic transmission and synchronized network activity, though neuronal morphology develops normally in its absence 4. Pathogenic CASK variants cause X-linked intellectual disability and microcephaly with pontocerebellar hypoplasia, representing a neurodevelopmental spectrum of variable severity 5. A large-scale resequencing screen identified CASK mutations in X-linked mental retardation families 6. Recent studies reveal that CASK-related disorder presents with tone abnormalities, sensorineural hearing loss, epilepsy, sleep difficulties, and cerebral visual impairment, with epilepsy significantly associated with intellectual disability severity 5. The high evolutionary conservation of CASK's coding sequence across species, despite its non-essentiality in invertebrates, underscores its critical importance for mammalian neurodevelopment 7.