PARP14 is a mono-ADP-ribosyltransferase that catalyzes the transfer of single ADP-ribose units from NAD+ onto glutamate residues on target proteins 1, distinguishing it from PARP1 and PARP2, which catalyze poly-ADP-ribosylation 2. PARP14 possesses dual enzymatic functions, including both transferase and hydrolase activities mediated through its macrodomain 1 3. Mechanistically, PARP14 regulates immune signaling by mono-ADP-ribosylating STAT proteins: it negatively regulates STAT1 phosphorylation to suppress pro-inflammatory cytokine production in macrophages 4, while positively enhancing STAT6-dependent transcription to promote IL-4-mediated macrophage activation 4. Following interferon stimulation, PARP14 mediates ADP-ribosylation within p62 bodies, requiring the ubiquitin-proteasome system and involving its E3 ligase partner DTX3L 5. Clinically, PARP14 shows neuroprotective effects in stroke models, where increased expression inhibits microglial activation via LPAR5 suppression and promotes functional recovery 6. Additionally, PARP14 participates in lipid metabolism regulation with pathophysiological roles in metabolic disorders including fatty liver disease and atherosclerosis 7. PARP14 also functions in antiviral immunity, with SARS-CoV-2's Mac1 hydrolase counteracting PARP14-mediated ADP-ribosylation 3.