Correctors of the basic trafficking defect of the mutant F508del-CFTR that causes cystic fibrosis

• Many correctors of the trafficking defect of mutant CFTR have been identified.
• The targets and mechanism of action of most correctors are unknown.
• Pharmacological chaperones and proteostasis modulators are defined.
• Some correctors are in clinical trials.

Cystic fibrosis (CF) is the most frequent lethal genetic disease and the most frequent mutation is F508del-cystic fibrosis transmembrane regulator (CFTR). In common with some other protein trafficking diseases the mutant protein is functional but recognized by the cellular quality control system retained in the endoplasmic reticulum (ER) and degraded. There have been some recent impressive advances in developing corrector compounds that restore the trafficking of the mutant protein to the plasma membrane. The targets of these correctors and possible mechanisms of action are discussed.