Numerous studies have shown that loss-of-function mutations in TREX1 lead to abnormal accumulation of cytoplasmic DNA, which in turn over-activates the natural immune response and ultimately leads to the development of autoimmune diseases, including systemic lupus erythematosus and vascular diseases, retinopathy, and cerebral leukoencephalopathy (59, 60). Here, TREX1 is linked to autoimmune disease.