Ceramides are products of fat and protein metabolism that accumulate in individuals prone to metabolic disorders. Once ceramide levels rise above a critical level threshold, tissues such as skeletal muscle, adipose, and the liver become unresponsive to insulin, the hormone that drives postprandial nutrient uptake and storage. The Summers Laboratory found that implementing pharmacological or genetic engineering strategies to block ceramide accumulation in rodents improves insulin sensitivity and prevents the onset of diabetes, fatty liver disease, and various cardiovascular complications. Building upon these discoveries, they now seek to understand the regulatory mechanisms governing ceramide synthesis or action and to identify new therapeutic strategies for reducing ceramides to treat these diseases.