The inhibition of ENaC, when combined with CFTR modulators, has the potential to act as a synergistic driving force for Cl− secretion via rescued mutant CFTR channels in airway epithelial cells, offering a promising avenue for enhancing airway surface hydration, mucociliary clearance, and overall pulmonary outcomes in CF patients and other muco-obstructive lung diseases. This evidence concerns the gene CFTR and cystic fibrosis.