BRF1 (TFIIB-related factor 1) is a general transcription factor essential for RNA polymerase III (Pol III) transcription initiation 1. The protein functions as a core component of the TFIIIB complex, with isoform 1 directing Pol III transcription of tRNA, 5S RNA, and adenovirus VA1, while isoform 2 specifically regulates U6 promoter transcription 1. BRF1 expression is transcriptionally regulated by multiple factors including estrogen receptor alpha (ERα), Sp1, and Runx2, which control Pol III gene expression levels [PMID:28972307; 2; 36]. BRF1 is significantly overexpressed in estrogen receptor-positive breast cancer, where it correlates with enhanced translational capacity and cell proliferation [PMID:28972307; 47]. Environmental factors including alcohol and carcinogens upregulate BRF1 expression through ROS-mediated signaling pathways [PMID:31781337; 55]. BRF1 mutations cause cerebellofaciodental syndrome and are associated with neurodegenerative diseases, highlighting its developmental importance 1. Conditional Brf1 deletion in adult epithelial tissues induces apoptosis and disrupts organ homeostasis, demonstrating its essential role in tissue maintenance 6. However, BRF1 overexpression alone is insufficient to initiate tumorigenesis, suggesting a permissive rather than oncogenic role 6. BRF1 serves as a biomarker for breast cancer diagnosis and prognosis, and represents a potential therapeutic target.