Cystic fibrosis transmembrane conductance regulator (F508del) (F508del-CFTR)

ΔF508-CFTR refers to the cystic fibrosis transmembrane conductance regulator (CFTR) protein carrying the deletion of phenylalanine at position 508, which is the most prevalent mutation causing cystic fibrosis (CF) [1, 3]. This mutation primarily results in a Class II processing defect where the protein misfolds and is prematurely degraded by the endoplasmic reticulum-associated degradation (ERAD) pathway, preventing its trafficking to the apical cell membrane [2, 12]. Even when small amounts of the mutant protein reach the surface, it exhibits impaired gating and reduced stability [2, 4]. The resulting deficiency in chloride and bicarbonate transport leads to dehydrated, viscous secretions that obstruct the airways and ducts of the lungs, pancreas, and other organs [3, 7]. Therapeutic intervention involves CFTR modulators, including 'correctors' that stabilize the protein's structure to allow trafficking and 'potentiators' that enhance the activity of the channel at the cell surface [5, 21]. Modern triple-combination therapies (e.g., elexacaftor/tezacaftor/ivacaftor or vanzacaftor/tezacaftor/deutivacaftor) have significantly improved clinical outcomes for patients with at least one F508del allele [8, 19, 21].

Other names

ΔF508-CFTRdeltaF508-CFTRPhe508del-CFTRClass II CFTR mutation

CFTR modulators act as either correctors or potentiators. Correctors (e.g., lumacaftor, tezacaftor, elexacaftor, vanzacaftor) facilitate the proper folding and cellular trafficking of the misfolded ΔF508-CFTR protein from the endoplasmic reticulum to the plasma membrane. Potentiators (e.g., ivacaftor, deutivacaftor) increase the open-channel probability of CFTR at the cell surface to enhance anion transport.