CFTR with F508del mutation is a protein that does not mature, is unable to reach the plasma membrane, has a defect in the transport of chloride and is unstable in the membrane. To correct these defects it is therefore necessary the combined use of molecules able to induce the normal maturation of the protein (correctors), activate its function (potentiators) and stabilize it. This project starts from the hypothesis that the combinations of drugs currently used for the recovery of CFTR-F508del have on average little effectiveness because they do not respond to the need for stability of CFTR in the membrane. This stability depends very much on the interaction that the protein, once reached the membrane, must have with important constituents of the cell membrane. The project intends to investigate the possibility that the ganglioside GM1, an important component of the cell membrane, probably deficient in the CF bronchial epithelial cells, can increase the efficiency of correctors and potentiators in the functional recovery of CFTR with F508del mutation. The project starts from preliminary data showing that the combination of GM1 with Lumacaftor and Ivacaftor (Orkambi) is able to increase the function of F508del-CFTR in CF bronchial epithelial cells. It also intends to study how GM1 modifies the interactions between CFTR and other membrane proteins, to favor their stability and therefore its intensity and duration of the function. The GM1 would have the advantage of being already in use for other diseases (neurodegenerative in particular).