Evidently, the most promising target forpotential therapy basedon PNP inhibitors is the human enzyme (hPNP).9−11 A rare autosomal-recessivemetabolic disease caused by mutated and functionally deficient PNPis characterized by severe depletion of T-cells and, thus, by immunodeficiency.PNP deficiency results in an accumulation of its physiological substrate2′-deoxyguanosine (dGuo), which is sequentially phosphorylatedby deoxycytidine/deoxyguanosine kinase (dCK/dGK) and nucleotide kinasesup to dGuo triphosphate (dGTP). Here, PNP is linked to immunodeficiency disease.