Interferon gamma-inducible protein 16 (IFI16)

Interferon gamma-inducible protein 16 (IFI16) is a member of the HIN-200 (hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats) family and functions as a sensor for intracellular DNA of pathogenic or damaged cellular origin. It contains both DNA-binding domains and pyrin domains required for protein-protein interactions and inflammasome function. IFI16 plays a pivotal role in the innate immune response by detecting viral and aberrant DNA, which triggers production of type I interferons and other pro-inflammatory cytokines via the IRF3/NF-κB pathway. It interacts with key cell cycle regulators (e.g., p53, RB1), regulates cell proliferation, and can mediate several forms of regulated cell death, including pyroptosis, apoptosis, and necroptosis (collectively known as PANoptosis), particularly relevant to infectious and inflammatory diseases. IFI16 also participates in the host restriction of herpesviruses through the silencing of viral gene expression via chromatin remodeling and inflammasome activation. Dysregulation of IFI16 has been linked to autoimmune diseases, inflammatory disorders, and malignancies. Direct drug targeting of IFI16 remains an area of future therapeutic interest.

Other names

Gamma-interferon-inducible protein Ifi-16Interferon-inducible myeloid differentiation transcriptional activatorPYHIN2IFNGIP1

No approved drugs directly target IFI16; mechanism for hypothetical therapy would likely be modulation of DNA sensing, interferon induction, or inflammasome activity.