What ion channel defect causes cystic fibrosis?

Cystic fibrosis is caused by defects in the CFTR ion channel, encoded by the CFTR gene.

CFTR stands for cystic fibrosis transmembrane conductance regulator. It is an epithelial-cell membrane protein that functions mainly as a chloride and bicarbonate channel. By controlling anion movement, CFTR helps regulate salt and water on surfaces lining the airways, pancreas, intestine, and other organs. When CFTR function is impaired, these secretions become abnormally thick and sticky.

More than 1,800 CFTR variants have been identified, although only some cause cystic fibrosis. The most common disease-causing variant is F508del, historically written ΔF508. It removes phenylalanine at position 508, causing the protein to misfold and be destroyed before reaching the cell surface. Other variants can reduce channel opening, production, or stability. The CFTR gene was identified in 1989 by a team led by Lap-Chee Tsui.

A common misconception is that CFTR is simply a chloride pump. It is an ATP-regulated ion channel, and its dysfunction also alters sodium and water transport indirectly. The resulting airway mucus, pancreatic disease, and elevated sweat chloride are central features of cystic fibrosis.