Harnessing the 14-3-3 protein–protein interaction network

Protein–protein interactions (PPIs) play a critical role in cellular signaling and represent interesting targets for therapeutic intervention. 14-3-3 proteins integrate many signaling targets via PPIs and are frequently implicated in disease, making them intriguing drug targets. Here, we review the recent advances in the 14-3-3 field. It will discuss the roles 14-3-3 proteins play within the cell, elucidation of their expansive interactome, and the complex mechanisms that underpin their function. In addition, the review will discuss significant advances in the development of molecular glues that target 14-3-3 PPIs. In particular, it will focus on novel drug discovery and development methodologies that have delivered selective, potent, and drug-like molecules that could open new avenues for the development of precision molecular tools and medicines.