POLR2G (RPB7) is a core dissociable subunit of RNA polymerase II that functions as part of a heterodimer with POLR2D/RPB4. This subcomplex binds to the clamp element of Pol II and locks it in a closed conformation, preventing double-stranded DNA from entering the active site while allowing single-stranded DNA and RNA binding 1. POLR2G is essential for vertebrate development and survival; polr2d-deficient zebrafish embryos showed progressive developmental delays beginning at 11 hours postfertilization, with diminished housekeeping and zygotic gene expression ultimately leading to premature death 1. Beyond its structural role in transcription, POLR2G has emerged as a pathogenic target gene in gestational diabetes mellitus (GDM), identified through integration of gene expression and DNA methylation data 23. POLR2G was identified as a hub gene with high diagnostic potential in GDM patients through protein-protein interaction and ROC analysis 3. Additionally, POLR2G serves as a direct target of miR-34a-5p in Huntington's disease pathogenesis and is affected by miR-624 in hepatocellular carcinoma progression 45. These findings suggest POLR2G's involvement extends beyond canonical transcription to encompass metabolic disease and neurodegeneration, positioning it as a potential biomarker and therapeutic target.