EFEMP1 (EGF-like fibulin extracellular matrix protein 1) encodes fibulin-3, an extracellular matrix glycoprotein with diverse biological functions. The protein binds to the epidermal growth factor receptor (EGFR), inducing autophosphorylation and activating downstream signaling pathways 1. EFEMP1 modification by the CA19-9 glycan enhances its interaction with EGFR, leading to hyperactivation of EGFR signaling in pancreatic disease models 1. In hepatic stellate cells, EFEMP1 is among core genes upregulated during activation and fibrosis development, particularly in metabolic dysfunction-associated steatohepatitis 2. The gene plays critical roles in ocular health, with mutations associated with multiple inherited retinal diseases including Doyne honeycomb retinal dystrophy, autosomal dominant drusen, and various macular dystrophies 34. EFEMP1 variants are also linked to glaucoma and myopia 5. Additionally, circulating EFEMP1 protein levels may serve as a biomarker for diabetic complications and aging-related processes 67. The protein's involvement in extracellular matrix organization and EGFR signaling positions it as a potential therapeutic target across multiple disease contexts.