ZNF469 is a zinc finger transcription factor that regulates collagen and extracellular matrix (ECM) gene expression across multiple tissues. 1 ZNF469 binds directly to gene bodies and regulatory elements to control collagen production in hepatic stellate cells, emerging as a key determinant of liver fibrosis in metabolic dysfunction-associated steatotic liver disease. 2 In dermal fibroblasts, ZNF469 acts as a putative transcriptional regulator of collagen biosynthesis and functions downstream of NRF2, a master antioxidative regulator. 3 ZNF469 knockdown impairs fibroblast proliferation, migration, and collagen production while suppressing ECM-related gene expression, indicating its central role in fibroblast function and ECM homeostasis. ZNF469 mutations cause Brittle Cornea Syndrome, a condition characterized by ECM disruption in corneal tissues. 4 Recent studies reveal unexpected associations between ZNF469 variants and aortic/arterial aneurysms and dissections, suggesting broader roles in vascular ECM integrity. 5 At the molecular level, ZNF469 contains intrinsically disordered regions and forms biomolecular condensates, though endogenous protein localization differs from overexpressed protein. 6 In lung adenocarcinoma, ZNF469 upregulation correlates with poor prognosis and altered immune infiltration, suggesting disease-specific functional complexity. 7