SCNN1A encodes the alpha subunit of the epithelial sodium channel (ENaC), a critical component for sodium ion transport across epithelial membranes 1. The primary function involves sodium ion homeostasis and regulation of blood pressure through renal sodium reabsorption 2. Mechanistically, SCNN1A mutations can cause either loss-of-function, leading to pseudohypoaldosteronism type 1 with salt wasting and hyperkalemia 1, or gain-of-function, resulting in Liddle syndrome characterized by hypertension and hypokalemia 23. The p.Phe226Cys mutation causes an 83% reduction in ENaC activity through decreased protein expression and reduced channel open probability 1. Disease relevance extends beyond electrolyte disorders, as SCNN1A is overexpressed in pancreatic cancer where it promotes cell proliferation, migration, and invasion 4. It also serves as a prognostic biomarker in triple-negative breast cancer, with high expression associated with poor neoadjuvant chemotherapy response 5. Additionally, SCNN1A polymorphisms are linked to neonatal respiratory distress syndrome in term infants 6. Clinical significance includes its potential as a therapeutic target and biomarker across multiple diseases, from inherited electrolyte disorders to cancer metastasis 7.