PARP9 (poly(ADP-ribose) polymerase family member 9) is an ADP-ribosyltransferase that functions primarily in immune responses and DNA damage repair through its association with the E3 ubiquitin ligase DTX3L. PARP9 serves as a noncanonical RNA virus sensor in dendritic cells and macrophages, recognizing viral RNA and activating the PI3K/AKT3 pathway to promote type I interferon production independently of the MAVS pathway 1. In immune signaling, PARP9 regulates PARP14 activity through protein-protein interactions and its macrodomain hydrolytic activity, controlling interferon-induced ADP-ribosylation 2. The PARP9-DTX3L complex enhances DTX3L's E3 ligase activity and mediates NAD+-dependent mono-ADP-ribosylation of ubiquitin, preventing ubiquitin conjugation to substrates like histones 2. During DNA repair, PARP9 is recruited to damage sites via binding to ribosylated PARP1, facilitating recruitment of DNA repair factors including 53BP1, BRCA1, and promoting non-homologous end joining 2. PARP9 is frequently overexpressed in human breast cancer, where it promotes cell migration and is associated with lymph node metastasis 3. The protein has been identified as a potential diagnostic biomarker for inflammatory bowel disease and ischemic stroke 4 5. Clinical significance includes its potential as a therapeutic target in cancer immunotherapy and viral infections.