POLR1G encodes RNA polymerase I subunit G, a core component of mammalian RNA polymerase I essential for ribosomal RNA (rRNA) transcription. POLR1G functions as a critical structural subunit within the RNA polymerase I preinitiation complex (PIC), directly interacting with other regulatory proteins including PinX1 and PAF53 to enable rDNA transcription initiation and elongation 1. The protein localizes to nucleolar and nucleoplasmic compartments where it facilitates transcription of nucleolar large rRNA 2. Mechanistically, POLR1G assembly into the PIC is regulated by post-translational modifications of binding partners. Upon nutrient starvation, acetylation of PinX1 disrupts its interaction with POLR1G, leading to PIC disassembly and shutdown of ribosome biogenesis as an energy-conservation strategy 1. This regulatory mechanism links cellular nutrition status to nucleolar transcription control. Clinically, POLR1G variants show disease associations predominantly through genetic interaction studies. POLR1G polymorphisms interact with IL1B and smoking duration to influence lung cancer susceptibility in East Asian populations 2. Additionally, POLR1G appears in monoadduct DNA repair pathways, with germline variations potentially associated with melphalan treatment outcomes in cancer therapy 3. High PinX1 expression in colorectal cancers correlates with POLR1G-dependent ribosome biogenesis dysregulation, suggesting therapeutic targeting potential through PIC assembly disruption 1.