Cystic fibrosis transmembrane conductance regulator protein (CFTR)

The cystic fibrosis transmembrane conductance regulator protein (CFTR) is an ATP-binding cassette (ABC) transporter-class anion channel expressed on the apical (surface) membrane of epithelial cells in organs such as the lung, pancreas, gastrointestinal tract, and sweat glands. Unique among ABC transporters, CFTR primarily functions as a passive ion channel, facilitating regulated transport of chloride and bicarbonate ions across epithelial membranes to help maintain salt and water homeostasis. The CFTR protein comprises five major functional domains: two transmembrane domains (TMD1 and TMD2) forming the channel pore, two cytosolic nucleotide-binding domains (NBD1 and NBD2) involved in ATP binding/hydrolysis, and a regulatory (R) domain controlling channel gating via phosphorylation. Mutations in the CFTR gene underlie cystic fibrosis and other exocrine disorders; these mutations can affect protein synthesis, folding, trafficking, channel conductance, and regulation. Therapeutic targeting of CFTR exploits potentiators, which increase ion channel opening, and correctors, which improve CFTR folding/trafficking to the membrane—transforming treatment for patients with select CFTR mutations.

Other names

CFTR proteinCystic fibrosis transmembrane conductance regulatorATP-Binding Cassette Subfamily C Member 7ABCC7Cystic fibrosis transmembrane conductance regulator channel

Potentiation (increasing channel open probability); Correction (improving folding, trafficking, and surface expression); Stabilization of channel gating; Combination therapy (potentiator + corrector)