Abstract: Methods and compositions are provided for determining intracellular translocation of proteins employing ?-galactosidase fragments that independently complex to form an active enzyme. Cells are used having two fusion constructs: one fragment bound to a protein of interest; and the other fragment bound to a compartment localizing signal. The cells are used to screen compounds for their effect on translocation, where a substrate containing high ionic strength solution is used for detection of the enzyme complex.