The project aims to investigate the mechanisms that regulate the function of the CFTR protein on the cell membrane, believing that the limited effectiveness of CFTR modulators available today is due to the fact that they are the result of a wide molecule screening and not the product based on knowledge of the normal and altered mechanisms of CFTR function. The project aims to deepen the action of a peptide developed by the research group, permeable to cells and derived from the enzyme PI3Kγ, which works as a CFTR activator, significantly more effective than the currently available CFTR potentiators. The peptide not only opens the CFTR channel but, at the same time, preserves its expression to the plasma membrane, where it exerts its function. The project aims to explore the activity of PI3Kγ at various levels: the maturation of CFTR, its membrane stabilization, the opening of the channel and the chain of molecular events that regulate it, the interaction with other membrane proteins and the hypothesized action on other chloride channels other than CFTR. All this should help to understand the complex functioning of the molecular machine dedicated to regulating the hydro-salt balance of epithelia and seriously compromised in FC, with the intent to open the way to more rational therapies of the basic defect.