CNTNAP1 encodes contactin-associated protein 1 (Caspr1), a transmembrane protein essential for myelinated axon organization and function. The protein localizes to paranodal regions flanking nodes of Ranvier in both peripheral and central nervous systems, where it forms a complex with contactin-1 and neurofascin-155 to establish proper axonal domain organization 1. CNTNAP1 is critical for maintaining paranodal junctions and enabling saltatory conduction of action potentials along myelinated nerve fibers 2. Pathogenic variants in CNTNAP1 cause severe congenital hypomyelinating neuropathy characterized by hypotonia, respiratory distress, joint contractures, and high infant mortality 3. Disease-associated mutations lead to protein instability, reduced surface expression, retention in neuronal soma, and disrupted paranodal ultrastructure with everted myelin loops 2. The condition affects both peripheral and central nervous systems, with surviving patients often requiring mechanical ventilation and experiencing seizures 3. Currently, 54 individuals with biallelic CNTNAP1 variants have been reported, demonstrating phenotypic diversity but consistent key features including intellectual disabilities and reduced life expectancy 4. Experimental gene therapy approaches in mouse models show promise for treatment by restoring proper axonal domain organization 2.