ZNFX1 is a multifunctional RNA-binding protein that acts as a double-stranded RNA sensor to initiate innate immune responses against viral pathogens 1. The protein recognizes viral dsRNA and interacts with innate immune signaling pathways to restrict RNA virus replication 2. Beyond antiviral defense, ZNFX1 functions as a negative regulator of the NLRP3 inflammasome, suppressing excessive inflammation by retaining NLRP3 in the cytoplasm and preventing its activation 3. The protein also regulates mRNA stability of apoptosis-related genes, protecting cardiomyocytes from ischemic injury 4. ZNFX1 operates as a ubiquitin E3 ligase with a split active site mechanism, clustering single-stranded RNA into ubiquitin-coated nucleoprotein particles 2. Loss-of-function mutations in ZNFX1 cause immunodeficiency 91, characterized by severe viral susceptibility, multisystem inflammation, and hemophagocytic lymphohistiocytosis-like disease 1. Mechanistically, ZNFX1 deficiency impairs interferon-stimulated gene expression and reduces viral clearance capacity 1. The protein also serves as a tumor suppressor in ovarian and lung cancers through inflammasome signaling and transcriptional regulation 5, 6. These findings reveal ZNFX1 as a master regulator balancing antiviral immunity with inflammatory control.