This invention provides compositions and methods for restoring proper folding and function of Cystic Fibrosis Transmembrane Conductance Regulator mutant with in-flame-deletion of phenylalanine 508 (AF508 CFTR). The invention also provides methods for identifying novel agents capable of restoring proper folding and function of ΔP508 CFTR. The invention additionally provides methods for treating cystic fibrosis.