Mono-ADP-ribosylation (MARylation), which is catalyzed by mono-ARTs such as PARP3, PARP6–PARP12 and PARP14–PARP16, tunes the activity of targets involved in fundamental cell processes and various signaling pathways, ranging from those regulating cell survival and proliferation to those modulating the cellular response to stress and viral infection. Here, PARP16 is linked to viral infectious disease.