E3 ubiquitin ligase WWP2 as a promising therapeutic target for diverse human diseases.

Mammalian E3 ubiquitin ligases have emerged in recent years as critical regulators of cellular homeostasis due to their roles in targeting substrate proteins for ubiquitination and triggering subsequent downstream signals. In this review, we describe the multiple roles of WWP2, an E3 ubiquitin ligase with unique and important functions in regulating a wide range of biological processes, including DNA repair, gene expression, signal transduction, and cell-fate decisions. As such, WWP2 has evolved to play a key role in normal physiology and diseases, such as tumorigenesis, skeletal development and diseases, immune regulation, cardiovascular disease, and others. We attempt to provide an overview of the biochemical, physiological, and pathophysiological roles of WWP2, as well as open questions for future research, particularly in the context of putative therapeutic opportunities.