BRF2 (TFIIB-related factor 2) is a general transcription factor and exclusive component of TFIIIB required for RNA polymerase III transcription of genes with upstream promoter elements, particularly type 3 promoters driving transcription of U6, RNase P, and 7SK RNAs 1. As a TFIIIB subunit, BRF2 recruits RNA polymerase III to type 3 promoters and functions as a transcriptional activator under normal conditions 1. During transcription initiation, BRF2 blocks template DNA in the RNA-DNA hybrid; its retraction is essential for the transition from initiation to elongation 1. BRF2 responds to cellular stress: it downregulates target genes and protects cells against oxidative stress-induced apoptosis [UniProt]. Pathologically, BRF2 is frequently overexpressed in multiple cancer types and functions as an oncogene. In invasive breast carcinoma, BRF2 alterations occur in 21% of cases and correlate with significantly decreased overall survival 2. In lung cancers, BRF2 upregulation promotes squamous carcinoma cell survival via SLC8A3-mediated mitochondrial homeostasis and reduced apoptosis 3, while it enhances adenocarcinoma proliferation and metastasis through MAPK/ERK pathway activation 4. Conversely, biallelic loss-of-function BRF2 variants cause severe neurodevelopmental disease with perinatal death and craniofacial anomalies, reflecting critical roles in RNA polymerase III function and development 5.