the rearrangement of the transmembrane helices. This changes the accessibility of the cargo binding site from an inward-facing position to an outward facing one. ATP binding, and the hydrolysis that follows, drives the alternative exposure of the cargo binding site, ensuring a unidirectional transport of cargo against an electrochemical gradient. In CFTR, alternating between an inward-facing conformation to an outward-facing one results in channel gating. In particular, NBD dimerization (favored by ATP binding) is coupled to transition to an outward-facing conformation in which an open transmembrane pathway for anions is formed. Subsequent hydrolysis (at the canonical active site, site 2, including Walker motifs of NBD2) destabilizes the NBD dimer and favors return to the inward-facing conformation, in which the anion permeation pathway is closed off. The CFTR is found in the epithelial cells of many organs including the lung, liver, pancreas, digestive tract, and the female and male reproductive tracts. In the airways of the lung, CFTR is most highly expressed by rare specialized cells called pulmonary ionocytes. In the skin, CFTR is strongly expressed in the sebaceous and eccrine sweat glands. In the eccrine glands, CFTR is located on the apical membrane of the epithelial cells that make up the duct of these sweat glands. Normally, the protein allows movement of chloride, bicarbonate and thiocyanate ions (with a negative charge) out of an epithelial cell into the Airway Surface Liquid and mucus. Positively charged sodium ions follow passively, increasing the total electrolyte concentration in the mucus, resulting in the movement of water out of the cell via osmosis. In epithelial cells with motile cilia lining the bronchus and the oviduct, CFTR is located on the apical cell membrane but not on cilia. In contrast, ENaC (Epithelial sodium channel) is located along the entire length of the cilia. In sweat glands, defective CFTR results in reduced transport of sodium chloride and sodium thiocyanate in the resorptive duct and therefore saltier sweat. This is the basis of a clinically important sweat test for cystic fibrosis often used diagnostically with genetic screening. Interactions Cystic fibrosis transmembrane conductance regulator has been shown to interact with: DNAJC5, GOPC, PDZK1, PRKCE, SLC4A8, SNAP23, SLC9A3R1, SLC9A3R2, and STX1A, It is inhibited by the anti-diarrhoea drug crofelemer. Related conditions Congenital bilateral absence of vas deferens: Males with congenital bilateral absence of the vas deferens most often have a mild mutation (a change that allows partial function of