POLR2H is a shared structural subunit of RNA polymerases I, II, and III, essential for transcription of diverse gene classes including ribosomal RNA precursors, mRNA, and functional non-coding RNAs 1. The protein functions as a core component of the RNA polymerase II complex and participates in transcription elongation and termination across all three polymerase types 2. Mechanistically, POLR2H interacts with cofactors such as glutaminase 1 (GLS1), which acts as a chaperone affecting RNA polymerase II complex assembly in the nucleus 1. The protein also associates with cellular factors involved in RNA splicing and protein translation 3. POLR2H has emerged as a prognostic biomarker in multiple malignancies: elevated expression correlates with prostate cancer progression, cell migration, and proliferation, with associations to immune cell infiltration suggesting immunotherapy relevance 4. In lung cancer, POLR2H is identified as a hub gene associated with patient survival 2. Additionally, POLR2H appears as a diagnostic gene in co-occurring COPD and lung adenocarcinoma, with altered expression detected in these conditions 5. In viral infections, POLR2H functions in antiviral responses during HIV and monkeypox co-infection through innate immunity activation 6. These findings position POLR2H as both a fundamental transcriptional regulator and an emerging therapeutic target across diverse disease contexts.