In addition, the pathway is controlled by specialized enzymes acting as negative regulators: the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) mediates the degradation of the STING ligand cGAMP (154, 155); and the levels of tumor-derived DNA, as the upstream stimulus of cGAS, are negatively controlled through the three-prime exonuclease 1 (TREX1) by cytosolic DNA degradation (156) (Figure 3). Here, ENPP1 is linked to neoplasm.