In vitro and in vivo models of CF were used to demonstrate whether treatment of CF cells and CF mice with potential protein kinase CK2 modulators are able to play a role in the process leading to premature degradation of CFTR-F508del protein. Data were shown indicating that pharmacological inhibition of CK2 prolongs the rescue effect of cysteamine after its whashout. Refining existing leads through a target-driven drug discovery approach may be useful to identify old/new and more efficacious compounds which favour a better and larger rescue of mutant CFTR.