Thus, VEXAS can be viewed as an acquired, age-intensified proteasomeopathy in which somatic UBA1 dysfunction meets declining proteostatic capacity and epigenetic myeloid bias, igniting a self-perpetuating circuit of proteotoxic stress, type I-interferon-driven autoinflammation, and clonal myeloid dominance. The gene discussed is UBA1; the disease is VEXAS syndrome.