SCN2B encodes the β2 subunit of voltage-gated sodium channels (VGSCs), serving as a regulatory component that modulates channel trafficking, localization, and biophysical properties 1. The β2 subunit promotes cell surface expression of sodium channel α subunits and is essential for proper channel function in excitable tissues 1. In cardiac tissue, SCN2B plays critical roles in establishing normal electrical activity, with deletion studies in mice demonstrating reduced sodium and potassium current densities in ventricular myocytes and conduction slowing in the right ventricular outflow tract 2. Loss of SCN2B function results in both ventricular and atrial arrhythmias, with increased susceptibility to atrial fibrillation, elevated fibrosis levels, and higher repolarization dispersion 2. The protein's primary mechanism involves chaperoning voltage-gated sodium channel α-subunits to the plasma membrane, similar to its neuronal function 2. Clinically, SCN2B variants are associated with cardiac arrhythmias including atrial fibrillation and have been implicated in Brugada syndrome 2. Polymorphisms in SCN2B show associations with epilepsy risk, particularly idiopathic epilepsy 3. The gene has also been identified as a potential biomarker in HIV-associated encephalitis and myocardial bridging 45.