PathHunter® Pharmacotrafficking cell lines are engineered to co-express a ProLink™ (PK)-tagged transmembrane protein retained in the ER (due to protein misfolding), and an Enzyme Acceptor (EA) tag localized to the endosomes. Binding of a chemical pharmacochaperone to the misfolded, PK-tagged protein stabilizes the protein in a conformation that enables itstrafficking through the Golgi, then onward to the cell membrane. Protein re-localized to the cell membrane subsequently internalizes (either passively or actively) into EA-tagged endosomes, forcing complementation of the two β-galactosidase enzyme fragments (EA and PK). The resulting functional enzyme hydrolyzes substrate to generate a chemiluminescent signal.