EREG encodes epiregulin, a ligand for the epidermal growth factor receptor (EGFR) and ERBB4 that plays critical roles in cellular signaling, tissue development, and disease pathogenesis 1. Unlike other EGFR ligands such as EGF, epiregulin induces weaker, asymmetric EGFR dimers that produce sustained signaling and promote differentiation rather than proliferation 2. This unique signaling pattern is disrupted in glioblastoma, where mutations prevent EGFR from discriminating between ligands, allowing epiregulin to form strong EGF-like dimers 1. EREG expression is dysregulated in various cancers, where it activates EGFR signaling pathways to promote tumor progression 3. In head and neck squamous cell carcinoma, EREG stability depends on STT3B-mediated N-glycosylation, which is essential for its membrane localization and ability to upregulate PD-L1 via the c-myc pathway, facilitating immune evasion 4. Beyond cancer, EREG serves important developmental functions, enhancing differentiation of human intestinal organoids by promoting formation of enteric neurons, endothelial cells, and organized smooth muscle 5. During embryo implantation, EREG processed by ADAM12 enhances decidualization, demonstrating its role in reproductive biology 6. These diverse functions highlight EREG's significance as both a developmental regulator and potential therapeutic target.