Anti-inflammatory treatments that abate the decline in pulmonary function in CF patients are needed. Because altered ceramide levels are involved in CF lung disease, targeting different pathways in sphingolipid (SL) metabolism, with the final goal to reduce ceramide, represents a therapeutic tool for limiting the excessive lung inflammation in CF patients. In this regard, several inhibitors have been proposed. Researchers addressed their interest to the iminosugar marketed drug miglustat (Zavesca) that produces an anti-inflammatory effect in CF bronchial cells, by targeting β-glucosidase 2 (GBA2). Iminosugars offer many advantages as potential drug candidates, due to their good oral bioavailability and very specific immune modulatory and chaperoning activity. This proposal is aimed to analyze miglustat-derivative iminosugars as anti-inflammatory drugs for CF lung-disease. The most promising derivatives will be then validated in CF primary human airway cells and in murine models of lung inflammation.