In addition to pathogen-derived dsDNA, cGAS is also activated by self-DNA, like mitochondrial DNA (mtDNA) and nuclear DNA that are aberrantly localized in the cytosol or in the micronuclei under pathophysiological conditions, including mitochondrial stress, genomic instability, and/or DNA damage, leading to sterile inflammation associated with various diseases such as autoimmune diseases, cancers, and metabolic dysfunctions (Li and Chen, 2018; Bai and Liu, 2019; Figure 1). The gene discussed is CGAS; the disease is cancer.