CFTR function measurement is required for screening of potential CFTR correctors/potentiators and human models are needed, in particular for preclinical studies and personalized medicine. Upon validation of European Cystic Fibrosis Society, Intestinal Current Measurements (ICM) Standardized Operating Procedure (SOP) will be utilized in Verona for diagnosis of atypical cases in addition to nasal potential difference (NPD) already available. Further rectal organoids and leukocytes of subjects tested by ICM and/or NPD will be tested for CFTR function. The aims of our project will be to detect the effects on CFTR function of new molecules targeting F508del mutation, to test CFTR function in organoids (derived from stem cells by rectal biopsies) and by ICM, leukocytes assay and NPD in the same subjects. Molecules targeting F508del mutation provided by the Cystic Fibrosis Foundation Therapeutics will be tested. Effects of new drugs on CFTR function could be detected in the same CF patient using four different methods. CFTR function in the presence of mutations of uncertain clinical relevance will be tested in leukocytes and rectal organoids beside standardized ICM and NPD. This study proposes a relatively simple and robust assays to facilitate diagnosis, functional studies, drug development as well as personalized medicine approaches in CF.