Cystic fibrosis (CF) is a lethal genetic disease most frequently caused by a F508del mutation in the cystic fibrosis transmembrane regulator (CFTR), a chloride ion transport channel. Mutant F508del-CFTR is flagged for proteolytic degradation by the protein quality control machinery in the endoplasmic reticulum (ER), preventing its trafficking to the plasma membrane and leading to the CF disease state. If the mutant F508del-CFTR protein reaches the plasma membrane it is still functional as a chloride channel and, therefore, an attractive approach to treating CF would be the use of small molecule ‘correctors’ that rescue the trafficking of F508del CFTR protein to the plasma membrane. This WEBinar will describe our use of a Chemical Genetics approach to discover the sponge natural product latonduine A, a potent F508del-CFTR trafficking corrector. It will also describe in detail how we have identified its novel dual protein target mechanism of action. Latonduine A is a promising lead compound for developing a new class of F508del-CFTR trafficking corrector drugs.