MAPDA (N6-methyl-AMP deaminase) is a cytosolic deaminase that catalyzes the detoxification of modified adenosines arising from RNA degradation. The enzyme acts downstream of adenosine kinase to hydrolyze N6-methylated adenosine nucleotides, including N6-methyl-AMP (m6AMP), N6,N6-dimethyl-AMP (m6,6AMP), and N6-isopentenyl-AMP (i6AMP), converting them to inosine monophosphate (IMP) 12. MAPDA exhibits broad substrate specificity, removing various alkyl groups from N6- and O6-substituted purine nucleoside monophosphates 3. Modified nucleosides derived from mRNA, rRNA, and tRNA degradation possess inherent cytotoxicity; MAPDA prevents their accumulation and metabolic dysfunction 1. The enzyme contains a catalytic zinc ion and plays a critical role in a multilayer molecular protection system that prevents erroneous incorporation of N6-methylated nucleotides into nascent RNA, since eukaryotic RNA polymerase can utilize N6-mATP as a substrate 2. Functionally, MAPDA mutations reduce enzyme activity and can confer resistance to nucleotide-based therapeutics by impairing their intracellular activation 4. The evolutionary distribution of MAPDA correlates with the prevalence of m6A-RNA methylation across eukaryotic organisms 2.