As much as 85% of the human proteome is considered to be undruggable as many proteins lack well-defined pockets for small-molecule drugs to bind and modulate their function. This has been challenged with the emergence of targeted protein degradation approaches, that make use of the cytosolic waste disposal system for the removal of a disease-causing protein, ablating all of its functions. However, such strategies have been limited to target engagement within the intracellular environment.