PWP1 (periodic tryptophan protein 1) is a WD-40 repeat-containing chr12-associated protein that functions as a key regulator of ribosome biogenesis and growth control. Primary Function: PWP1 regulates RNA polymerase I (Pol I)-mediated transcription of large rRNAs (5.8S, 18S, 28S) and coordinates with Pol III-mediated 5S rRNA transcription 12. It epigenetically maintains rDNA loci in a transcription-competent state through histone H4K20me3-dependent mechanisms 13. Mechanism: PWP1 responds to nutrient-dependent mTOR signaling, controlling nucleolar localization and TFIIH recruitment to regulate ribosomal gene expression 1. In telomere maintenance, PWP1 stabilizes the shelterin complex via WD40 domains and regulates H4K20me3 levels 3. Disease Relevance: PWP1 is frequently overexpressed in multiple human cancers. In colorectal cancer, elevated PWP1 drives growth through ribosome biogenesis 4. In gastric cancer, PWP1 transcriptionally regulates p53, promoting proliferation and suppressing apoptosis 5. In lung cancer, PWP1 enhances Wnt signaling and inhibits Hippo signaling via interactions with DVL2 and Merlin 6. Clinical Significance: High PWP1 expression correlates with poor prognosis in head and neck squamous cell carcinoma and lung cancer, representing a potential therapeutic target 16.