PROTACs (Proteolysis-targeting chimeric molecules) artificially hijack the components of the UPS to degrade a target protein. PROTAC drugs are hetero-bifunctional small molecules that contain two functional ligands connected via a linker; one ligand binds to a target protein and the other ligand binds to an E3 ligase. Bringing these two entities into proximity theoretically leads to polyubiquitylation and proteasomal degradation of the target protein. However, given the complexity this scenario does not always play out, and the PROTAC discovery strategy faces several challenges and pitfalls. To address these challenges, LifeSensors developed high-throughput tools for monitoring both polyubiquitylation and degradation of a target protein. Measuring ubiquitylation of a protein in a plate-based format accelerates PROTAC-based drug discovery. We have developed several platforms that enable rapid, quantitative monitoring of in vitro as well as cellular ubiquitylation.