Many effective pharmaceutical drugs are small molecules that work by attaching to or otherwise interacting with proteins in the body that contribute to disease. Unfortunately, many devastating diseases—including Alzheimer’s disease, Parkinson’s disease, and insulin-resistant diabetes—are driven by proteins that are considered “undruggable” because they have flexible structures that do not reliably interact with small-molecule drugs and often end up in aggregated clumps. GRIPs aims to transform the way we drug these “undruggable” proteins by editing pieces of the protein’s chemistry that change how they behave and clump together. The researchers will develop a suite of targeted "protein editors” that work by pairing “editing” enzymes that already exist in the body with drugs approved for different purposes. GRIPs enable existing enzymes to get close enough to misfunctioning proteins to do their jobs and increase their efficacy. The project will initially focus on four specific proteins of interest but aims to create a new treatment platform that can address difficult-to-treat disorders across body systems.