TREX1

TREX1 is an endoplasmic-reticulum-associated 3′-5′ exonuclease that degrades a broad range of aberrant cytosolic DNA species, including DNA derived from retroelements, stalled replication intermediates, micronuclei, and mitochondrial stress. By clearing this DNA before it accumulates, TREX1 acts as a nucleolytic safeguard that keeps the cGAS-STING DNA-sensing pathway from being inappropriately activated by the cell’s own DNA. Loss-of-function mutations in TREX1 cause Aicardi-Goutières syndrome, a monogenic type I interferonopathy driven by unchecked cGAS-STING signaling.