CFTR is an ATP-binding cassette transporter that uniquely functions as an ion channel on epithelial cell membranes 1. Its primary function is regulating epithelial ion and water transport through chloride-selective anion conductance 2. CFTR mediates chloride ion transport across the cell membrane using ATP hydrolysis to gate channel opening, with the regulatory (R) domain blocking the intracellular vestibule until PKA phosphorylation enables channel activity 1. The channel is also permeable to bicarbonate, with selectivity depending on extracellular chloride concentration 34. Beyond direct ion transport, CFTR modulates other ion channels and transporters, including inhibition of the epithelial sodium channel (ENaC) and regulation of bicarbonate transporters 567. Clinically, CFTR dysfunction causes cystic fibrosis, the most common lethal genetic disease in Caucasians, resulting from impaired airway fluid homeostasis and compromised pathogen defense 28. The most prevalent mutation is ΔF508, occurring in ~70% of CF alleles in Northern Europe and North America 9. CFTR mutations also cause congenital bilateral absence of the vas deferens and infertility through disrupted epididymal electrolyte secretion essential for sperm maturation 10. Understanding CFTR's structural basis for channel function, distinct from other ABC transporters, is crucial for developing targeted therapeutics.