PRPS2 (phosphoribosyl pyrophosphate synthetase 2) is an X-linked enzyme that catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP), a crucial intermediate in nucleotide biosynthesis 1. Located at Xp22.2-p22.3, PRPS2 shares 95% sequence identity with PRPS1 but exhibits distinct regulatory properties 2. Unlike PRPS1, PRPS2 is less sensitive to allosteric inhibition due to four non-conserved residues that bypass typical ADP/GDP feedback inhibition, enabling sustained ATP production 3. The enzyme forms hexameric structures that can polymerize into filaments, with polymerization being essential for catalytic activity 2. PRPS2 demonstrates significant clinical relevance across multiple cancers. In acute lymphoblastic leukemia, therapy-induced PRPS2 mutations contribute to drug resistance and relapse 4. In lung cancer, PRPS2 is upregulated and promotes proliferation, migration, and invasion while inhibiting apoptosis 5. The enzyme also stabilizes MAT2A to enhance SAM synthesis for RNA m6A methylation, linking nucleotide metabolism to epigenetic regulation 3. In osteosarcoma, elevated PRPS2 expression correlates with poor prognosis and tumor recurrence 6. Additionally, PRPS2 upregulation in Sertoli-cell only syndrome inhibits apoptosis through p53/Bcl-2/caspase signaling pathways 7. These findings establish PRPS2 as both a potential biomarker and therapeutic target across various malignancies.