GJB1 encodes connexin32, a gap junction protein that forms intercellular channels for small molecular transport between neighboring cells 1. In myelinating Schwann cells and oligodendrocytes, GJB1-formed gap junctions are critical for axonal homeostasis and maintenance of myelin integrity 1. Mutations in GJB1 cause X-linked Charcot-Marie-Tooth disease type 1 (CMTX1), the second most common inherited neuropathy, affecting over 400 documented variants 1. Most pathogenic GJB1 variants impair functional gap junction formation or produce channels with abnormal biophysical properties, leading to demyelinating neuropathy in animal models 1. CMTX1 presents as progressive sensory and motor neuropathy with males (52% of affected individuals) experiencing moderate-to-severe symptoms and neurophysiologically demonstrating intermediate conduction slowing and distal axonal degeneration 2. Females are typically less severely affected and progress more slowly than males over extended periods 2. Disease progression is measurable, with moderate responsiveness at 3 years post-baseline, enabling assessment in clinical trials 2. Among CMT cases, GJB1 mutations account for approximately 13% of genetic diagnoses 3. Current management remains supportive, though genetic therapy approaches targeting GJB1 expression are under investigation 4.