EXOG is a mitochondrial endo/exonuclease that functions as a critical enzyme for maintaining mitochondrial DNA (mtDNA) integrity through multiple DNA processing pathways. Primary function: EXOG exhibits 5'-3' exonuclease activity with preference for single-stranded DNA and possesses a Wing domain that suppresses endonuclease activity while conferring precise dinucleotide excision capability 1. Mechanism: EXOG processes DNA intermediates through three major pathways: (1) removal of single-stranded DNA flaps generated during base excision repair 2, (2) processing of RNA primers during mtDNA replication, including cleavage at RNA-DNA junctions and cooperation with RNase H1 34, and (3) removal of deoxyribose phosphate (dRP) lesions and abasic sites during base excision repair 5. EXOG's Wing domain enables substrate specificity distinct from its paralog EndoG, which differentiated during metazoan evolution 6. Disease relevance: EXOG participates in mtDNA depletion responses to herpes simplex virus infection through redundant mechanisms with ENDOG 7. Clinical significance: EXOG's multifunctional role in mtDNA maintenance positions it as important for conditions involving mitochondrial dysfunction, though direct clinical associations require further investigation.