NUDT12 is a mammalian Nudix hydrolase that functions as a specialized mRNA decapping enzyme with distinct substrate preferences and cellular roles. The protein primarily operates as an NAD-cap decapping enzyme, specifically removing nicotinamide adenine dinucleotide (NAD) caps from mRNAs by hydrolyzing the diphosphate linkage to produce nicotinamide mononucleotide and 5' monophosphate mRNA 1. NUDT12 functions exclusively as homodimers, with each monomer contributing to the formation of two functional catalytic pockets 2. The enzyme shows preferential activity toward reduced nicotinamide nucleotides (NADH, NADPH) over oxidized forms, with Km values of 11μM for NADH and 190μM for NAD+ 3. NUDT12 localizes to peroxisomes via a C-terminal PNL targeting signal and forms a large dodecamer complex with bleomycin hydrolase (BLMH) in discrete cytoplasmic granules distinct from P-bodies 32. The enzyme plays important regulatory roles in cellular metabolism, particularly responding to nutrient stress by targeting NAD-capped transcripts encoding proteins involved in cellular energetics 1. Loss of Nudt12 leads to significant upregulation of circadian clock transcripts in mouse liver, indicating its involvement in circadian regulation 2. Additionally, NUDT12 shows disease associations, being upregulated in diabetic peripheral neuropathy and showing differential methylation patterns in essential hypertension 45.