CFTR and cystic fibrosis: The most common disease-associated allele, a three base pair deletion in NBD1 (F508del), is found in ~87% of people with CF where it disrupts CFTR folding by at least two mechanisms: (i) directly inhibiting NBD1 folding efficiency and/or stability4–6; and (ii) destabilizing an intramolecular interface between NBD1 and the 4th intracellular loop (ICL4) in TMD26–8.