TRPT1 (tRNA phosphotransferase 1) is a bifunctional enzyme with dual catalytic activities. Its canonical function involves catalyzing the final step of tRNA splicing by transferring the 2'-phosphate from ligated tRNA to NAD+, producing ADP-ribose 1''-2'' cyclic phosphate 1. The human TRPT1 gene, located at chromosome 11, encodes a 253-amino acid protein conserved across eukaryotes and bacteria 1. Beyond tRNA processing, TRPT1 functions as an ADP-ribosyltransferase capable of modifying nucleic acids. It ADP-ribosylates phosphorylated ends of both RNA and DNA, representing a novel non-canonical RNA capping mechanism 2. This modification is reversible through ADP-ribosylhydrolases including PARG, TARG1, MACROD1/2, and ARH3 3. Structural studies reveal that TRPT1 employs distinct catalytic residues for tRNA 2'-phosphotransferase versus ADP-ribosylation activities, with flexibility in nucleic acid substrate binding 4. Clinically, TRPT1 has emerged as a bipolar disorder risk gene through fine-mapping genome-wide association studies 5, suggesting involvement in neurotransmission or neurodevelopment. Evidence indicates mammalian TRPT1 promotes HeLa cell survival and proliferation 4. The physiological significance of nucleic acid ADP-ribosylation likely encompasses DNA repair, antiviral immunity, and cellular stress responses 6.