F508del, the most frequent mutation in CF, causes a severe stability and maturation defect of CFTR protein. There are already drugs, named correctors, for the treatment of CF patients with F508del. However, present correctors show modest efficacy. The hypothesis here is that mutant CFTR protein is still degraded to a large extent, despite the treatment with correctors, due to the activity of quality-control (QC) proteins named ubiquitin ligases (UBLs). UBLs act as controllers of protein production. They recognize CFTR with the F508del mutation as a defective protein and hence attach ubiquitin, a sort of molecular tag that causes protein degradation. Importantly, there are also other types of QC proteins, named deubiquitinases (DUBs), that remove the ubiquitin tag and therefore save proteins from degradation. There are approximately 100 different DUB types in human genome. The aim of the current project is to identify the UBLs and DUBs that determine the fate of mutant CFTR. Researchers have already identified DUB and UBL proteins whose silencing causes a modification of mutant CFTR function. They will analyze the mechanisms of action associated with these effects using complementary techniques that can clarify the type of interaction (physical and/or functional) between such proteins and CFTR. The identification of proteins that control mutant CFTR degradation will be important to design novel pharmacological strategies.