Glycosphingolipids are a class of membrane lipids that regulate numerous cellular processes, including membrane organization, proliferation, cell cycle regulation, apoptosis, transport, migration, and inflammatory signaling.1 Dysregulation of this critical pathway in polycystic kidney disease (PKD) was first reported several decades ago. In the cpk/cpk mouse model, which exhibits renal pathology similar to human autosomal recessive PKD, levels of glucosylceramide (GL-1) and lactosylceramide were greater, ceramide levels were higher, and glucosylceramide synthase (GCS) activity was elevated as compared to control kidneys, suggesting the sphingolipids may play a role in disease progression (Fig 1).