POLR2B encodes the second largest subunit of RNA polymerase II (RPB2), a core component of the transcriptional machinery essential for DNA-templated RNA synthesis. As part of the RNA Pol II complex, POLR2B participates in transcription initiation and elongation at protein-coding genes 1. Beyond canonical transcription, POLR2B interacts with regulatory proteins; for example, PRKDC recruits POLR2B to hepatitis B virus cccDNA to promote viral transcription through kinase-dependent mechanisms 2. POLR2B also functions in circRNA-mediated regulation, where m6A-modified circPOLR2B forms R-loop structures with its parental gene to modulate transcription output 3. In disease contexts, POLR2B dysregulation is clinically significant. POLR2B overexpression in glioblastoma promotes tumor cell growth; conversely, POLR2B knockdown suppresses proliferation in vitro and tumor growth in xenograft models, identifying it as a potential therapeutic target 1. POLR2B was identified as a diagnostic biomarker for diabetic nephropathy through machine learning analysis of metabolism-related genes and correlates with immune cell infiltration patterns 4. Additionally, POLR2B expression is dysregulated in colorectal carcinoma, particularly in African American patients with altered DNA methylation patterns 5. These findings establish POLR2B as both a fundamental transcriptional component and a disease-relevant biomarker.