PPAT (phosphoribosyl pyrophosphate amidotransferase) catalyzes the formation of phosphoribosylamine from PRPP and glutamine, serving as the rate-limiting enzyme in de novo purine biosynthesis (DNPB) 12. Operating in the cytosol, PPAT functions as part of the purinosome, a metabolic complex involved in efficient purine nucleotide generation 1. Beyond its catalytic role, PPAT serves a scaffolding function through protein-protein interactions; specifically, NUDT5 interaction with PPAT promotes PPAT oligomerization and suppresses its enzymatic activity during purine salvage, facilitating purinosome disassembly and balancing DNPB with salvage pathways 13. In disease contexts, PPAT upregulation drives aberrant purine metabolism in hepatoblastoma through β-catenin-dependent transcriptional activation, promoting cell proliferation and migration 2. PPAT mutations occur in microsatellite-unstable gastric and colorectal cancers, suggesting metabolic reprogramming contributions to oncogenesis 4. Additionally, PPAT emerges as a glutamine metabolism-related biomarker in diabetic foot ulcer pathogenesis 5. Disrupting NUDT5-PPAT interactions induces thiopurine drug resistance by permitting excessive DNPB despite purine salvage 1, highlighting PPAT's clinical relevance in cancer chemotherapy response and metabolic disease progression.