In the 1-year pilot project (FFC#1/2018) researchers identified a number of proteins that, if silenced in CF cell models, trigger a relevant CFTR-F508del rescue. The aims of this extension project are: 1) to identify the most promising proteins to be tested as potential pharmacological targets; 2) to verify and validate the findings in primary cell lines from F508del patients; 3) as a parallel activity, to introduce and validate for CF research an extremely advanced analytical protocol, that may allow to simultaneously track the spatial localization of thousands of proteins in a living cell. As far as this technique of spatial proteomics is concerned, researchers will implement the LOPIT technique, developed by Prof. Kathryn Lilley’s group (University of Cambridge), enrolled as collaborator. The potential impact of this project on the CF community is thought to be relevant in terms of increased number of targets that may be immediately transferable into a bigger number of options for drug discovery activities.