Z-DNA binding protein 1 (ZBP1) belongs to a family of proteins that contain the Zalpha domain which binds specifically to left-handed Z-DNA and Z-RNA. ZBP1 was initially identified as a novel gene that was up-regulated in activated macrophages in mice bearing ascites tumors, suggesting that is may play a role in processes such as host response in neoplasia. More recent reports indicate that the cytosolic ZBP1 has can act like the toll-like receptor TLR9 by detecting cytosolic double-stranded (ds) DNA and trigger induction of type I interferon and other innate immune responses. It is thought that the binding of ZBP1 to dsDNA enhances its association with innate immune response proteins such as the IRF3 transcription factor and the serine/threonine kinase TBK1 (also known as NAK). Multiple isoforms of ZBP1 are known to exist.