CFTR and cystic fibrosis: With the advent of ‘highly effective’ CFTR-directed therapeutics in the clinics, and the fact that clinical trials of CFTR modulators demonstrated heterogeneous responses in clinical outcomes as well as sweat Cl− levels among individuals with the same CF genotypes [24,26,28,80], additional sensitive biomarkers of CFTR function are critical to understand the degree of functional rescue of CFTR mutations by different CFTR modulator drugs, both at the level of CFTR genotype groups as well as individual’s responsiveness.