Cyclic GMP-AMP synthase (cGAS, MB21D1) is an antiviral enzyme that produces the second messenger cyclic-GMP-AMP (cGAMP) in response to cytoplasmic DNA. The cGAS protein acts as a cytosolic DNA sensor that binds DNA and produces the cGAMP second messenger from ATP and GTP. cGAMP binds to and activates STING, a transmembrane adaptor protein that is a critical component of the cellular innate immune response to pathogenic cytoplasmic DNA. STING is ubiquitously expressed and found predominantly in the ER. Following activation, STING translocates with TBK1 to perinuclear endosomes. The TBK1 kinase phosphorylates and activates interferon regulatory factors (IRFs) and NF-kappaB, which leads to the induction of type I interferon and other immune response genes.