CFTR and cystic fibrosis: The clinical use of combinations of small-molecule modulators targeting the functional defects in different mutant CFTR protein variants significantly improved lung function, and as a result, the lives and life expectancies have markedly improved for many patients with cystic fibrosis (CF).82 As “proof of concept,” this remarkable therapeutic response to molecular modulation of a dysfunctional transporter (CFTR) suggests that a similar approach may have clinical benefit in patients with cholestasis associated with variant hepatobiliary transporters.