Z-DNA-binding protein 1 (ZBP1)

Z-DNA-binding protein 1 (ZBP1) is a cytosolic innate immune sensor that recognizes double-stranded nucleic acids (both DNA and RNA) adopting the left-handed Z-conformation (Z-DNA, Z-RNA), a structural form often produced during viral infections or cellular stress[1][2][3][4]. Upon binding Z-nucleic acids through its N-terminal Zα domains, ZBP1 initiates a cascade of immune and cell death responses—serving as a key activator of apoptosis, necroptosis, pyroptosis (PANoptosis), and type I interferon production, largely through protein–protein interactions with RIPK3, MLKL, caspase-8, and inflammasome components[2][4][1][3]. ZBP1 is highly induced by interferons and viral infection, conferring resistance to viruses but, if dysregulated, contributing to inflammatory diseases and potentially cancer. No approved drugs target ZBP1 directly, but pharmacologic interest exists, and ZBP1 pathway modulation may provide therapeutic benefits or safety risks depending on context[2][4].

Other names

DAIDLM-1DNA-dependent activator of IFN-regulatory factorsTumor stroma and activated macrophage protein DLM-1DNA-dependent activator of IRFsC20orf183dJ718J7.3

Activation (or inhibition) of ZBP1 leads to modulation of cell death pathways (apoptosis, necroptosis, pyroptosis) via interaction with RIPK3, MLKL, caspase-8, and inflammasome activation[4][2]. Upstream modulation through induced interferon signaling[2].