In recent years, the co-opting of ubiquitin ligases by small molecules for the targeted protein degradation of disease-causing proteins has emerged as a powerful pharmacologic modality. While the discovery of PROTACs has become a mainstay of drug discovery, discovery of novel molecular glue degraders particularly beyond CRBN modulators remains a major challenge for the field. I will present recent work on understanding the principles that govern molecular glue interactions, updates on our discovery platforms and recent examples of success to target novel and previously undruggable neo-substrates and to expand the repertoire of ligases enabled for molecular glues.