POLR1F (RNA Polymerase I Subunit F) is a core component of RNA Polymerase I, the enzyme responsible for synthesizing ribosomal RNA (rRNA) precursors 1. As part of the Pol I complex, POLR1F functions in multiple stages of rRNA transcription, including transcription initiation, elongation, and termination. The protein likely participates in recruitment of Pol I to rDNA promoters through its association with RRN3/TIF-IA, with interaction regions between RRN3 and POLR1F being evolutionarily conserved across species 1. Beyond its canonical ribosomal RNA synthesis function, POLR1F has emerged as a critical oncogenic factor in anaplastic thyroid cancer (ATC). POLR1F is significantly upregulated in ATC tissues compared to normal thyroid samples, with the strongest gene dependency effect among Pol family members 2. Mechanistically, POLR1F promotes ATC proliferation and stemness by activating the F2R/p38 MAPK signaling pathway through H3K4 methylation-dependent transcriptional regulation 2. POLR1F knockdown substantially reduces ATC cell proliferation, colony formation, and tumor growth in both zebrafish and mouse xenograft models 2. These findings establish POLR1F as both an essential housekeeping gene for ribosome biogenesis and an actionable therapeutic target in aggressive thyroid cancer.