POLR2K is a shared subunit of RNA polymerases I, II, and III that catalyzes DNA-dependent transcription of diverse RNA species, including ribosomal RNA precursors, mRNA precursors, and non-coding RNAs 1. The protein functions as a core component of these polymerase complexes and exhibits DNA-directed RNA polymerase activity with zinc ion binding capability. POLR2K plays roles in transcription initiation, elongation, and termination across all three polymerase types and localizes to the nucleus and nucleolus 1. In cancer pathology, POLR2K demonstrates altered expression patterns associated with disease progression. The gene is amplified and overexpressed in multiple cancer types 2, and its expression is preferentially upregulated through alternative polyadenylation-mediated mechanisms in cancer tissues 3. POLR2K has been identified as a hub gene in mantle cell lymphoma coexpression networks 1 and as a pyroptosis-associated diagnostic biomarker in Parkinson's disease 4. Additionally, POLR2K expression is regulated by antioxidant signaling in response to hepatotoxic stress 5 and has been implicated in purine metabolism dysregulation associated with orbital inflammation 6. Clinically, POLR2K's involvement in transcriptional regulation positions it as a potential therapeutic target in various disease contexts, particularly in hematologic malignancies and neurodegenerative disorders where its dysregulation correlates with disease severity.