This is of particular interest in CF as responses to CFTR modulators have been highly variable between patients with the same CFTR genotype in clinical trials (Heijerman et al., 2019; Middleton et al., 2019), as well as in patient-derived samples (Dekkers et al., 2016), likely due to modifier genes and differences in the cellular environment. This evidence concerns the gene CFTR and cystic fibrosis.