Molecular chaperone proteins have evolved to support proper protein folding and mitigate pathological aggregation events. However, protein misfolding and aggregation is a hallmark of many myopathies and neurodegenerative diseases. This suggests that chaperone protein function is rendered ineffective under certain circumstances. Thus, understanding the molecular underpinnings of molecular chaperone function and dysfunction will inform drug discovery for a broad array of disorders including Huntington’s Disease and Parkinson’s Disease. In the Johnson Lab we employ chemical biology, biophysics, and biochemistry approaches to study conformationally dynamic molecular chaperones and uncover core structure-function relationships. With this information, we will discover strategies for activating chaperone function to treat protein misfolding diseases.