CFTR and cystic fibrosis: Cystic fibrosis (CF) is a lethal genetic disease that is primarily caused by misfolding of the cystic fibrosis transmembrane conductance regulator (CFTR), a polytopic membrane protein with two six-spanning transmembrane domains (TMD1, TMD2), two nucleotide-binding domains (NBD1, NBD2), and a relatively unstructured regulatory (R) domain1.