PARP11 is a mono-ADP-ribosyltransferase that catalyzes the transfer of ADP-ribose units to target proteins 12. The enzyme localizes to the nuclear envelope and plays roles in nuclear remodeling 3. Mechanistically, PARP11 inhibits type I interferon signaling by mono-ADP-ribosylating β-TrCP, an E3 ubiquitin ligase, which promotes IFNAR1 ubiquitination and receptor degradation 4. Additionally, PARP11 acts as an antiviral factor by cooperating with PARP12 to suppress Zika virus replication through degradation of viral NS1 and NS3 proteins, independent of its catalytic activity 5. PARP11 can also mono-ADP-ribosylate RNA at phosphorylated termini, a modification reversible by cellular hydrolases 6. Clinically, PARP11 represents a major immunosuppressive regulator in solid tumors. The enzyme is induced in tumor-infiltrating regulatory T cells and CD8+ cytotoxic T lymphocytes, where it promotes immunosuppression 78. Elevated PARP11 expression correlates with poor immunotherapy responses and reduced patient survival 9. Genetic or pharmacologic PARP11 inactivation using selective inhibitor ITK7 reverses immunosuppression, reinvigorates anti-tumor immunity, and significantly enhances CAR T cell and checkpoint inhibitor efficacy 78. These findings establish PARP11 as a potential biomarker and therapeutic target for cancer immunotherapy optimization.