ENDOV encodes endonuclease V, an inosine-specific ribonuclease that cleaves RNA at the second phosphodiester bond 3' to inosine residues 1, functioning on both single-stranded and double-stranded RNA substrates 1. The enzyme also cleaves inosine-containing tRNAs 1. Unlike bacterial homologs that target DNA lesions, human ENDOV exhibits RNA selectivity 2, recognizing 3 ribonucleotides upstream and 7-8 bp downstream of inosine cleavage sites 3. The catalytic mechanism involves two canonical and one regulatory Mn2+ ion coordinating the nucleophilic water 3. Biologically, ENDOV appears involved in immune regulation and cancer pathogenesis. ENDOV deletion in mice reduces chemically-induced hepatocellular carcinoma development, with reduced mRNA expression of cancer-related genes and dysregulated tRNA fragmentation 4. In atherosclerosis, ENDOV is upregulated in human carotid plaques 5 and promotes atherogenesis by enhancing monocyte recruitment to lesions 5. Clinically, ENDOV variants clustered with DNA repair genes in familial colorectal cancer cases 6, suggesting potential contribution to cancer predisposition. The tumor-suppressive phenotype in ENDOV-knockout mice warrants investigation in human hepatocellular carcinoma.