TREX1 (three prime repair exonuclease 1) is a major cellular 3'-to-5' DNA exonuclease that prevents autoimmunity by degrading cytosolic DNA species that would otherwise trigger innate immune responses 1. The protein functions as a critical negative regulator of the cGAS-STING pathway by metabolizing DNA fragments from endogenous retroelements and degrading cytosolic DNA that accumulates from damaged cellular organelles 23. TREX1's mechanism involves its localization to the endoplasmic reticulum membrane, which directs it to ruptured micronuclei where it degrades micronuclear DNA to limit cGAS activation and subsequent type I interferon production 4. Loss-of-function mutations in TREX1 cause Aicardi-Goutières syndrome, a severe inflammatory disease characterized by excessive type I interferon signaling, encephalopathy, and basal ganglia calcification 51. The clinical significance extends beyond rare genetic diseases, as TREX1 dysfunction contributes to systemic lupus erythematosus and other autoimmune conditions 1. Interestingly, TREX1 inactivation in cancer contexts can enhance antitumor immunity by unleashing STING-interferon signaling, suggesting therapeutic potential for cancer immunotherapy 6. The protein also participates in DNA repair processes and can be regulated by p53, which promotes TREX1 degradation to activate immune responses 3.