GMPR2 encodes guanosine monophosphate reductase 2, an enzyme that catalyzes the irreversible NADPH-dependent deamination of GMP to IMP 1. This enzymatic activity is critical for converting guanine nucleotides to adenine nucleotides and maintaining the intracellular balance between adenine and guanine nucleotides 1. GMPR2 represents a distinct isoform from GMPR1, showing 90% amino acid identity but differential tissue expression patterns 1. The enzyme exhibits Km values of 26.6 μM for NADPH and 17.4 μM for GMP 1. Structurally, GMPR2 forms a tetramer with each subunit adopting a (α/β)8 barrel fold, with GMP binding through interactions with specific residues that stabilize the flexible binding region 2. Beyond its metabolic role, GMPR2 functions in cellular differentiation, as overexpression promotes monocytic differentiation of HL-60 leukemia cells following TPA induction 3. Loss of GMPR2 expression is associated with basal-type breast cancer and correlates with poor patient outcomes 4. Additionally, GMPR2 has been implicated in Alzheimer's disease pathogenesis, showing decreased expression in disease models 5, and may serve as a potential therapeutic target for certain cancer subtypes 6.