POLR1B encodes a catalytic core component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase essential for ribosomal RNA synthesis 1. POLR1B participates in transcribing 47S pre-rRNA precursors from multicopy rRNA gene clusters, ultimately generating 5.8S, 18S, and 28S ribosomal RNAs 1. The protein functions throughout the complete Pol I transcription cycle—initiation, elongation, and termination—with POLR1B contributing to the active catalytic center by coordinating a magnesium ion and providing lysine residues that facilitate Watson-Crick base pairing during nucleotide incorporation 1. The enzyme exhibits high processivity while maintaining proofreading activity through POLR1H-mediated cleavage of misincorporated nucleotides 2. Clinically, POLR1B mutations cause Treacher Collins syndrome type 4 (TCS4), a rare autosomal dominant craniofacial disorder characterized by mandibular and malar hypoplasia 3. Pathogenic POLR1B variants induce p53-dependent apoptosis in the neuroepithelium, impairing neural crest cell migration and differentiation, as demonstrated in zebrafish models 3. Beyond craniofacial disease, POLR1B is upregulated in non-small cell lung cancer, where silencing suppresses proliferation and induces apoptosis 4. POLR1B also serves as a hub gene in colorectal and hepatocellular cancer pathways [PMID:33202381; 57], and shows differential expression in cluster headache patients 6.