Targeted protein degradation as a powerful research tool in basic biology and drug target discovery

Controlled perturbation of protein activity is essential to study protein function in cells and living organisms. Small molecules that hijack the cellular protein ubiquitination machinery to selectively degrade proteins of interest, so-called degraders, have recently emerged as alternatives to selective chemical inhibitors, both as therapeutic modalities and as powerful research tools. These systems offer unprecedented temporal and spatial control over protein function. Here, we review recent developments in this field, with a particular focus on the use of degraders as research tools to interrogate complex biological problems. Small molecules that hijack the cellular protein ubiquitination machinery to selectively degrade proteins of interest have emerged as therapeutic modalities and powerful research tools. This Review summarizes recent developments in this field, with a focus on the use of degraders as research tools.