NUDT9 (nudix hydrolase 9) is a mitochondrial enzyme that primarily functions as an ADP-ribose pyrophosphatase, hydrolyzing ADP-ribose (ADPR) to AMP and ribose 5'-phosphate 12. The enzyme also exhibits weak phosphohydrolase activity against NADH and FAD in vitro, though it shows higher specific activity toward ADPR compared to other substrates 2. NUDT9 operates as a monomer with a unique structure containing an N-terminal domain with a novel fold and a catalytic C-terminal Nudix domain, where substrate binding occurs in a cleft between these domains 1. The enzyme localizes exclusively to mitochondria, and its depletion results in increased respiratory chain activity and altered mitochondrial respiratory complex expression 2. NUDT9 shares 39% sequence identity with the C-terminal cytoplasmic domain of the TRPM2 calcium channel, though the TRPM2 domain has reduced enzymatic activity 1. Beyond its metabolic role, NUDT9 shows differential expression patterns in human endometrium during different menstrual cycle phases, with higher expression in epithelial glandular components than stromal components, suggesting involvement in cellular proliferation regulation 3. The precise regulation of cellular ADPR levels by NUDT9 is essential for controlling ADPR-mediated cellular processes 4.