CFTR encodes the cystic fibrosis transmembrane conductance regulator, an ATP-gated chloride channel that plays a crucial role in epithelial ion and water transport. The protein functions as a cyclic AMP-regulated, low conductance chloride channel in epithelial cells, utilizing ATP binding and hydrolysis to gate chloride ion transport across cell membranes 1. CFTR possesses an intrinsic ATPase activity and requires protein kinase A phosphorylation of its regulatory domain for channel opening 2. The channel is also permeable to bicarbonate ions, with selectivity dependent on extracellular chloride concentration. CFTR modulates the activity of other ion channels, including inhibiting epithelial sodium channels (ENaC) and regulating airway surface fluid composition, which is essential for defense against pathogens. Mutations in CFTR cause cystic fibrosis, the most common fatal hereditary disorder in Caucasians with an incidence of 1 in 2500-3500 live births 3. The most frequent mutation, ΔF508, occurs in approximately 70% of CF chr7 in Northern European populations 4. CFTR mutations also cause congenital bilateral absence of the vas deferens and affect male fertility 5. At the population level, gnomAD v4.1 classifies this gene as LoF-tolerant because heterozygous carriers are viable; this is distinct from clinical pathogenicity in disease contexts. Multiple CFTR modulators including ivacaftor, lumacaftor, and elexacaftor represent a therapeutic revolution, providing effective oral treatments for over 85% of patients 6.