RNGTT is a bifunctional mRNA-capping enzyme that catalyzes the first two steps of 5' cap synthesis on nascent mRNA transcripts. Its N-terminal domain removes the gamma-phosphate from the 5'-triphosphate end of nascent mRNA, while its C-terminal guanylyltransferase domain transfers the GMP moiety of GTP to create the characteristic 7-methylguanosine cap structure 1. This cap protects mRNA from degradation and recruits factors essential for RNA processing, splicing, export, and translation initiation 2. RNGTT expression is regulated by m6A methylation of its 3'UTR through the METTL3 methyltransferase, with RNGTT knockdown reducing ribosomal protein mRNA capping and disrupting mTOR signaling 3. Beyond mRNA maturation, RNGTT exhibits cytoplasmic capping-enzyme activity that regulates Hedgehog signaling by antagonizing protein kinase A, with this function conserved between Drosophila and mammalian cells 4. In zebrafish models, loss of rngtt impairs biliary epithelial cell transdifferentiation during liver regeneration by disrupting mTORC1 and DNA methylation regulation 5. Recent structural studies reveal that RNGTT docks to RNA polymerase II during co-transcriptional capping, coordinating with the paused transcription machinery to ensure proper cap synthesis 16. Aberrant RTE activation in cancer can disrupt RNGTT function, though the clinical significance of such disruptions remains incompletely understood 7.