Inflammatory syndromes often have overlapping clinical manifestations, making them difficult to diagnose and categorize. Using a genome-first approach, researchers at the National Institutes of Health (NIH) have discovered an inflammatory disease called vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic syndrome (VEXAS) that is caused by mutations in the UBA1 gene. In this episode, Peter Grayson, MD, MSc, a study author on the recent paper published in the New England Journal of Medicine, gives us further insight into the discovery of the VEXAS syndrome and the overall importance of rare rheumatic disease research at the genetic and molecular level.