The human proteome contains over 20,000 proteins, yet traditional small molecule drugs target fewer than 3,000, leaving vast therapeutic potential unexplored. Induced proximity approaches—including PROTACs, molecular glues, and other proximity-inducing molecules—represent a paradigm shift that expands the druggable proteome by leveraging cellular machinery rather than requiring direct target inhibition. However, systematic methods to identify and optimize proximity-inducing compounds remain limited. To address these challenges, we have developed complementary chemical biology platforms to systematically interrogate and expand the druggable proteome through induced proximity. In this talk, I showcase these platforms and their application to develop first-in-class degraders, and molecular glues for “difficult to drug” targets.