A cutting-edge analysis demonstrated that patients with somatic mutations in UBA1, a gene encoding the ubiquitin activating enzyme E1, developed treatment-refractory severe autoinflammatory conditions in late middle age, such as vacuole, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome (VEXAS) (124). This evidence concerns the gene UBA1 and VEXAS syndrome.