POLR3G encodes RNA polymerase III subunit G, a peripheral component of RNA polymerase III (Pol III) that catalyzes transcription of DNA into RNA 12. POLR3G is one of two mutually exclusive subunits (POLR3G or POLR3GL) that define alternative Pol III complexes, with POLR3G enriched in embryonic stem cells and transformed cells 34. The subunit acts as a long tether bridging Pol III components and coordinates stalk and clamp dynamics during transcriptional transitions, while occupying the active site to maintain autoinhibitory state in apo Pol III 25. POLR3G synthesizes small non-coding RNAs including 5S rRNA, tRNAs, and snRNAs from ~500 genomic loci, and regulates specific transcriptome subsets in pluripotent stem cells including protein-coding genes and microRNAs 16. Clinically, POLR3G is overexpressed in triple-negative breast cancer, where knockout impairs tumor growth and metastasis while inducing FOXA1 and androgen receptor expression 7. In bladder cancer, elevated POLR3G correlates with poor prognosis and promotes epithelial-mesenchymal transition via PI3K/AKT and Wnt signaling pathways 89. POLR3G is also required for DNA double-strand break repair through homologous recombination 10. Biallelic POLR3G variants have been identified in autism spectrum disorder cases, though functional mechanisms remain unclear 11.