PARP14

PARP14 (poly(ADP-ribose) polymerase 14) is a multidomain mono-ADP-ribosyltransferase that functions as both a writer and reader of ADP-ribosylation and regulates immunity, transcriptional control, and genome stability^[1][2]. Mechanistically, PARP14 acts as a transcriptional coactivator of STAT6, promoting IL-4/STAT6-dependent gene expression and supporting T helper 2 (Th2) differentiation, cytokine signaling, and allergic inflammatory responses^[3][4][5]. Through these activities, PARP14 links cytokine-driven transcriptional programs to immune-cell function and tissue inflammation^[3][4]. In disease settings, PARP14 contributes to allergic airway disease and has been implicated in cancer-associated survival pathways, including B-cell malignancies and hepatocellular carcinoma, where it supports cellular fitness and disease progression^[2][5][6]. Beyond immune regulation, PARP14 promotes homologous recombination and protects cells from replication stress, highlighting an additional role in maintaining genome integrity during DNA replication^[7]. Compared with related PARP isoforms, PARP14 is distinguished by the presence of multiple macrodomains together with a catalytic mono-ADP-ribosyltransferase domain, enabling it to integrate ADP-ribose recognition with ADP-ribose writing functions within a single protein^[1][2]. For experimental applications, selective PARP14 inhibitors such as RBN012759 have demonstrated high target selectivity and have been used to suppress PARP14-dependent ADP-ribosylation and attenuate allergic inflammatory phenotypes in vivo, providing useful pharmacological tools for mechanistic and translational research^[8][9].