The Tag-lite GPCR platform is now complemented with a universal quantitative functional GPCR internalization assay. The Tag-lite internalization assay is a b-arrestin and G-protein independent functional test. Validated on an increasing number of targets, this assay provides another readout to help researchers study and screen all classes of compounds: agonist, antagonist, inverse agonist, biased ligand, and agonist antibodies. The method is nondestructive, thereby enabling kinetic readout.