POLR1E is a subunit of RNA polymerase I (Pol I), the enzyme responsible for synthesizing ribosomal RNA precursors. It mediates interactions between Pol I and UBTF, a key transcription factor required for formation of the preinitiation complex at ribosomal DNA promoters. POLR1E is also involved in Pol I-specific functions including polymerase clustering to enhance the efficiency of rRNA gene transcription. Dysregulation of POLR1E expression has been associated with several diseases. Truncating variants in POLR1E were identified in three independent pedigrees with familial Hodgkin lymphoma 1. In multiple sclerosis, POLR1E expression is significantly elevated during acute clinical relapse compared to remission, suggesting POL1 pathway activation contributes to disease activity 2. In bladder cancer, POLR1E expression correlates with increased tumor stage and has potential diagnostic value 3. A genome-wide association study identified POLR1E as associated with lamotrigine treatment response in bipolar disorder 4. Additionally, altered expression of Polr1e was detected in a mouse model of Alzheimer's disease, implicating it in neurodegeneration pathways 5. These findings suggest POLR1E represents a potential therapeutic target in hematological malignancies, neurological disorders, and cancer, warranting further investigation into the molecular mechanisms linking Pol I function to disease pathogenesis.