CLCN1 encodes ClC-1, a voltage-gated chloride channel that generates most plasma membrane chloride conductance in skeletal muscle, stabilizing resting membrane potential and enabling action potential repolarization 1. The channel functions as a homodimer with double-barreled architecture: each subunit contains an independent ion conduction pathway controlled by fast glutamate gates, while a common slow gate regulates both subunits simultaneously, with significant open probability at resting potential further increasing upon depolarization [UniProt references]. ClC-1 exhibits chloride selectivity over other anions and maintains skeletal muscle excitability through regulated ion transport [UniProt references]. Loss-of-function CLCN1 mutations cause myotonia congenita, a nondystrophic myotonia characterized by delayed muscle relaxation, stiffness, pain, and weakness 2. Both autosomal dominant (Thomsen's disease) and recessive (Becker's disease) inheritance patterns occur, with ~130 known mutations 1. In a large German cohort (48 CLCN1 patients), myotonia occurred in 83.3%, myalgia in 57.4%, and cold-sensitivity was prominent; electromyography revealed myotonic runs in 89.1% 3. Cardiac involvement occurs in approximately 8-9% of patients, sometimes requiring pacemakers 3. Variant location predicts inheritance pattern: voltage-dependence alterations cluster in transmembrane domains one-two, loss-of-function variants in domains two-three, while intracellular domain variants show no dominant features 4. Mexiletine and lamotrigine provide symptomatic relief in approximately 50% of treated patients 3.