Sodium channel regulatory subunit beta-2

SCN2B encodes sodium channel regulatory subunit beta-2, a 24 kDa accessory protein that modulates voltage-gated sodium channels (Nav) by regulating their localization and functional activity (UniProt: O60939). The protein directly associates with multiple Nav channel subtypes including Nav1.1, Nav1.2, Nav1.3, Nav1.5, Nav1.6, Nav1.7, and Nav1.8, facilitating the selective passage of sodium ions across excitable membranes to initiate electrical signal propagation in cells and tissues. Beyond its neurological role, SCN2B is implicated in cardiac function; mutations cause familial atrial fibrillation (ATFB14; MIM 615378) characterized by disorganized atrial electrical activity (UniProt: O60939).

SCN2B shows decreased abundance in Alzheimer's disease brain tissue. Chaparral AD proteomics analysis of post-mortem AD brain compared to age-matched controls revealed downregulation of SCN2B across measured subcellular fractions, with a mean log2 fold-change of −0.31 (Chaparral AD proteomics). This reduction may reflect compromised neuronal excitability regulation or broader disruption of ion channel homeostasis in AD pathology, though the functional consequence remains to be clarified.