CFTR and cystic fibrosis: While cells heterologously expressing CF-causing variants remain very useful for CFTR studies, primary cell models can provide a more sensitive and reliable prediction of therapeutic responses for several reasons: (i) The last express CFTR in the native genomic context, while cell lines frequently use CFTR cDNA (a copy of the mature mRNA, which lacks the introns); therefore, cells lines may not recapitulate certain cellular mechanisms, including nonsense-mediated decay or splicing effects.