Targeted protein degradation in the transmembrane and extracellular space

Transmembrane and extracellular proteins play crucial roles in diverse cellular functions and communication, affecting the progression and treatment of various diseases by mediating vital cellular processes. Whereas targeted protein degradation (TPD) represents an advancing therapeutic modality that leverages cellular degradation machinery to eliminate proteins of interest, present strategies have been largely confined to intracellular targets. Now, emerging strategies toward transmembrane and extracellular proteins are rapidly expanding the horizon of this powerful technology. Here, we review TPD in the transmembrane and extracellular space (meTPD) and discuss platform technologies, features, applications, and limitations. We focus on the conceptual innovations used in developing the present meTPD technology as well as its potential value for biological research and therapeutic interventions.