NUDT3 is a versatile nudix hydrolase that functions as both an mRNA decapping enzyme and polyphosphate phosphatase, with substrate specificity determined by divalent cations 1. As a decapping enzyme, NUDT3 hydrolyzes the 5'-cap structure of specific mRNAs, particularly those involved in cell motility including integrin β6, lipocalin-2, and fibronectin, thereby regulating their stability and modulating breast cancer cell migration 2. The enzyme exhibits different enzymatic activities depending on metal cofactors: diphosphoinositol polyphosphate phosphohydrolase activity with magnesium, diadenosine hexaphosphate hydrolase activity with manganese, and endopolyphosphatase activity with zinc 1. Through its zinc-dependent polyphosphate degradation activity, NUDT3 plays a crucial role in protecting cells from oxidative stress and maintaining DNA integrity 1. The enzyme's decapping activity is regulated by inositol pyrophosphate signaling, specifically 5-InsP7, which inhibits NUDT3 and affects P-body dynamics and mRNA storage 3. NUDT3 has been linked to metabolic regulation through insulin signaling pathways and obesity 4. Additionally, NUDT3 appears relevant to neurodegenerative diseases like ALS/FTD, where altered polyphosphate metabolism contributes to disease pathogenesis 5.