CGAS (cyclic GMP-AMP synthase) is a nucleotidyltransferase that catalyzes formation of 2',3'-cyclic GMP-AMP (cGAMP) from ATP and GTP, functioning as a critical cytoplasmic DNA sensor in innate immunity 12. CGAS directly binds double-stranded DNA (dsDNA) of ≥40 bp length, inducing formation of liquid-like condensates that activate cGAMP synthesis 34. The produced cGAMP acts as a second messenger, binding and activating STING1 to trigger type-I interferon production 56. CGAS detects pathogenic dsDNA from DNA viruses and retroviruses (notably HIV-2) in the cytoplasm, enabling antiviral responses 57. Additionally, CGAS senses self-DNA released during cellular stress, mitochondrial dysfunction, DNA damage, and senescence, triggering sterile inflammation via STING1 8910. In healthy cells, nuclear CGAS remains inactivated through chr6 binding via nucleosome interaction, preventing autoimmunity 1011. CGAS also suppresses homologous recombination DNA repair by inhibiting PARP1 12. Recent studies implicate dysregulated cGAS-STING signaling in pulmonary fibrosis and atherosclerosis pathogenesis, suggesting therapeutic potential for pathway modulation 1314.