Abstract: The invention relates to a cystic fibrosis transmembrane conductance regulator (CFTR) modulator for use in the prevention and/or treatment of diseases involving endothelial and/or epithelial barrier dysfunctions. The disease does not comprise cystic fibrosis. The invention further relates to a pharmaceutical composition comprising a CFTR modulator as an active ingredient for use in the prevention and/or treatment of diseases involving endothelial and/or epithelial barrier dysfunctions. The invention further relates to a kit of parts for use in the prevention and/or treatment of diseases involving endothelial and/or epithelial barrier dysfunctions comprising i) a CFTR modulator and ii) a further CFTR modulator. The invention further relates to a method of treating a condition, disease or disorder involving endothelial and/or epithelial barrier dysfunctions in a subject, the method comprising administering a CFTR modulator to a subject, preferably a mammal, in the need thereof.