MACROD1 (mono-ADP ribosylhydrolase 1) functions as an ADP-ribosylhydrolase enzyme that removes mono-ADP-ribose modifications from proteins and other macromolecules. The protein demonstrates promiscuous enzymatic activity, efficiently removing ADP-ribose from 5' and 3'-phosphorylated double-stranded DNA adducts in vitro, and can also reverse mono-ADP-ribosylation of RNA mediated by various PARPs 12. MACROD1 is predominantly localized to mitochondria, particularly enriched in skeletal muscle tissue, where it appears crucial for maintaining mitochondrial morphology 13. The enzyme works alongside other ADP-ribosylhydrolases like MACROD2 and TARG1 to provide reversibility to mono-ADP-ribosylation signaling 3. Gene ontology analysis and interactome mapping suggest MACROD1's involvement in RNA metabolism within mitochondria 3. Dysregulation of MACROD1 expression has been associated with cancer pathogenesis, and recent studies have identified it as one of 25 key genes significantly associated with colorectal cancer liver metastasis 14. The protein's mitochondrial localization and promiscuous hydrolase activity have important implications for mitochondrial function and DNA damage regulation in vivo 1.