ENDOG (endonuclease G) is a mitochondrial nuclease that plays multiple critical roles in cellular homeostasis and genome stability. The enzyme functions as a DNA endonuclease that preferentially cleaves double-stranded DNA, particularly 5-hydroxymethylcytosine-modified DNA, and shows higher affinity for four-stranded Holliday junctions 1. ENDOG promotes autophagy through mTOR pathway suppression via phosphorylation-mediated interactions with YWHAG, leading to autophagy initiation 1. The protein also cleaves mitochondrial DNA in response to oxidative stress, inducing compensatory mtDNA replication 1. Importantly, ENDOG prevents genome instability by degrading extranuclear DNA species, including retrotransposon cDNA and long mtDNA fragments, while allowing formation of short nuclear mitochondrial DNA insertions 2. ENDOG regulates alternative splicing of key genes including Caspase-2 and hTERT through RNA cleavage mechanisms 34. In disease contexts, reduced ENDOG gene copy numbers are associated with male infertility and potential paternal mtDNA transmission 5. The enzyme also participates in caspase-independent apoptotic pathways, with age-related differences in expression affecting cellular responses to stress 6.