SCNN1B encodes the β-subunit of the epithelial sodium channel (ENaC), one of three pore-forming subunits critical for sodium homeostasis and fluid balance. ENaC mediates electrodiffusion of sodium ions across the apical membrane of epithelial tissues, with water following osmotically, particularly in the kidneys where it performs electrogenic sodium reabsorption 1. The channel is essential for airway surface liquid homeostasis, maintaining proper mucus clearance in the lungs 1. SCNN1B mutations cause distinct disease phenotypes. Gain-of-function mutations in SCNN1B cause Liddle syndrome, an autosomal dominant hypertension characterized by early-onset elevated blood pressure, hypokalemia, and suppressed plasma renin and aldosterone levels 23. Patients respond well to targeted amiloride therapy, an ENaC blocker 2. Loss-of-function SCNN1B mutations are associated with bronchiectasis and pseudohypoaldosteronism. Additionally, SCNN1B expression regulates human lung fibroblast proliferation and migration; reduced SCNN1B expression paradoxically increases fibroblast proliferation while decreasing migration and collagen deposition, potentially implicating SCNN1B in acute respiratory distress syndrome pathogenesis 4. Compensatory sodium reabsorption through SCNN1B contributes to diuretic resistance in certain conditions, as demonstrated in nephrotic syndrome where ENaC blockade combined with loop diuretics effectively restored fluid balance 5.