Rescuing the homeostasis of PRPS1 activity by controlling OGT-mediated O-GlcNAcylation or AMPK-mediated phosphorylation is a potential clinical prevention strategy for PRPS1 dysregulation-associated diseases, such as Arts syndrome, or for tumorigenesis and resistance to chemoradiotherapy in lung cancer. The gene discussed is PRPS1; the disease is lung cancer.