RRP15 is a nucleolar protein essential for ribosomal RNA (rRNA) processing and ribosome biogenesis 1. It localizes to the nucleolus and regulates both rRNA transcription and the maturation of 5.8S and large subunit rRNA, functioning in both pre-40S and pre-60S ribosomal subunit assembly 1. RRP15 is critical for nucleolar formation and checkpoint control; its depletion induces nucleolar stress that triggers the RPL5/RPL11/5S rRNA-Mdm2-p53 axis in p53-proficient cells (causing G1 arrest) or ATR-Chk1-mediated DNA damage responses in p53-deficient cells 1. Clinically, RRP15 is frequently upregulated in multiple cancers including colorectal cancer, esophageal cancer, pancreatic cancer, colon cancer, and hepatocellular carcinoma, where elevated expression correlates with poor prognosis 2345. RRP15 knockdown suppresses cancer cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) through ribosome stress pathways, including LZTS2-mediated β-catenin suppression in colorectal cancer and PATZ1-associated LAMC2/FAK pathway inhibition in hepatocellular carcinoma 25. Notably, RRP15 knockdown inhibits autophagy and induces apoptosis in pancreatic cancer cells 6. In a brain-specific context, RRP15 variants in excitatory neurons show protective associations with migraine risk 7. These findings position RRP15 as a potential therapeutic target, particularly in high-ribosome-biogenesis cancers.