Purine nucleoside phosphorylase (PNP) is a critical enzyme that catalyzes the phosphorolytic breakdown of the N-glycosidic bond in deoxyribonucleosides and ribonucleosides, producing free purine bases and pentose-1-phosphate, with preferential activity on 6-oxopurine nucleosides including inosine and guanosine 1. PNP functions as a central hub in purine salvage metabolism, regulating nucleotide availability and cellular homeostasis. Mechanistically, PNP activity constrains telomere length by controlling deoxyguanosine metabolism and dNTP substrate availability for telomerase 2, while reduced PNP expression allows inosine accumulation, which promotes drug resistance in lung cancer through adenosine A2aR signaling 3. During influenza A virus infection, viral proteins enhance PNP-mediated purine salvage, simultaneously promoting viral replication and host hyperinflammation; PNP inhibition shifts metabolism toward de novo synthesis, reducing both viral spread and pro-inflammatory signaling 4. PNP deficiency, a rare inherited disorder accounting for ~4% of severe combined immunodeficiency cases, causes profound T-cell dysfunction, recurrent infections, neurological complications in two-thirds of patients, and autoimmune manifestations in one-third, with accumulation of toxic metabolites like dGTP impairing cell division and neurologic function 5. The gene's therapeutic potential extends to anticancer strategies exploiting substrate specificity differences between bacterial and human PNP enzymes 6.