Delta F508 in cystic fibrosis: Willing but not able

Over 90% of cystic fibrosis patients carry at least one ΔF508 allele and approximately 50% are homozygous for the mutation. An intracellular trafficking defect prevents presentation of this mutated protein at the cell membrane. Once in the correct position, ΔF508CFTR can function as an ion channel. The processes involved in post-translational protein modifications are being unravelled. Mutations that disrupt these processes may be responsible for a large number of inherited conditions. Pharmacological manoeuvres aimed at correcting trafficking defects may allow us to utilise the functional potential of these abnormal proteins. Transgenic animal models will have an important role in this research. Gene replacement therapy is not the sole therapeutic end point of molecular medicine. As knowledge of the ΔF508 mutation expands, further strategies will develop to overcome the molecular defect. These will have clinical significance to most patients with cystic fibrosis.