PARP12 is a mono-ADP-ribosyltransferase that catalyzes mono-ADP-ribosylation (MARylation) of target proteins, serving diverse cellular functions. As an interferon-stimulated gene (ISG), PARP12 executes antiviral activities by suppressing Zika virus and alphavirus replication through direct ADP-ribosylation of viral proteins 1. Upon IFN-γ stimulation, PARP12 acts as a checkpoint regulating RIPK1 and RIPK3 MARylation to promote necroptosis while inhibiting apoptosis, with PARP12 deficiency enhancing antiviral responses against influenza 2. PARP12 regulates protein translation by localizing to stress granules through its RNA-binding domain, and modulates inflammation via association with p62/SQSTM1 1. In cartilage homeostasis, PARP12 promotes osteoarthritis progression by inhibiting PINK1/Parkin-dependent mitophagy through ISG15-mediated attenuation of mitofusin MFN1/2 ubiquitination and SUMOylation, with IRF1 transcriptionally upregulating PARP12 expression during inflammatory signaling 3. PARP12 also regulates basolateral protein transport via MARylation of GOLGA1 in a PRKD1-dependent cascade 3. Clinically, PARP12 was identified as a genetic risk factor for age-related macular degeneration through transcriptome-wide association analysis 4, suggesting roles in retinal health and suggesting potential therapeutic applications targeting PARP12 in inflammatory and degenerative diseases.