POLR1D encodes a shared subunit of RNA polymerases I and III that plays dual roles in development and disease 1. As a core component of these polymerases, POLR1D is essential for synthesizing ribosomal RNA precursors and small non-coding RNAs including 5S rRNA, snRNAs, tRNAs, and miRNAs 2. The protein functions by heterodimerizing with POLR1C to initiate assembly of multisubunit RNA polymerase complexes 1. Pathogenic POLR1D mutations cause Treacher Collins syndrome (TCS), a craniofacial ribosomopathy characterized by microtia, midface hypoplasia, micrognathia, and hearing loss 3. Disease mechanisms involve impaired rRNA synthesis and nucleolar dysfunction that selectively sensitizes cranial neural crest cells to p53-mediated apoptosis 4. Missense mutations like G52E reduce heterodimerization with POLR1C and impair rRNA production 5. Beyond developmental disorders, POLR1D is frequently overexpressed in colorectal and lung cancers 6, 7, 8. High POLR1D expression correlates with poor prognosis and promotes cell proliferation through Wnt-β-catenin and PI3K-Akt pathway activation 6, 8. Notably, POLR1D localizes to the cytoplasm where it interacts with mTORC1 regulators RAGA and RAPTOR, suggesting an unexpected role in nutrient sensing beyond transcription 1.