CNTNAP2 (contactin associated protein-like 2) is a scaffolding protein essential for organizing myelinated axons and forming functional neuronal domains critical for saltatory conduction 1. The protein demarcates the juxtaparanodal region of axo-glial junctions and likely participates in gap junction formation. CNTNAP2 plays a central role in early brain development, particularly in neuronal migration and interneuron specification 1. At the circuit level, CNTNAP2 maintains proper thalamocortical connectivity and social brain network organization 2, partly through oxytocin system regulation; Cntnap2 knockout mice exhibit reduced oxytocin-producing neurons in the paraventricular hypothalamus 3. Mechanistically, CNTNAP2 loss leads to reticular thalamic hyperexcitability, enhanced T-type calcium currents, and aberrant intrathalamic oscillations that drive autism-related behaviors 4. Mutations in CNTNAP2 cause cortical dysplasia and focal epilepsy (CDFE) syndrome with high autism spectrum disorder (ASD) penetrance 3. In humans, CNTNAP2 variants confer ASD susceptibility, though associations with specific polymorphisms (rs2710102, rs7794745) show weak to suggestive evidence 5. Notably, CNTNAP2-related neuromyotonia involves autoimmune targeting of CASPR2, a functionally related juxtaparanodal protein 6. Therapeutic interventions including oxytocin, reticular thalamic calcium channel blockers, and antipsychotics ameliorate behavioral deficits in animal models 134.