To date, four proteins have emerged as nuclear DNA sensors with critical roles in identifying and reacting to virus infection: interferon-inducible protein 16 (IFI16) (1, –, 3), interferon-inducible protein X (IFIX, also known as PYHIN1) (4, –, 6), cyclic GMP-AMP synthase (cGAS) (7, –, 10), and heterogenous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) (11). The gene discussed is PYHIN1; the disease is viral infectious disease.