EPHA3 (EPH receptor A3) is a transmembrane receptor tyrosine kinase that mediates cell-cell communication through binding of membrane-bound ephrin ligands, triggering bidirectional forward and reverse signaling 12. The receptor preferentially binds ephrin-A ligands, particularly EFNA5, regulating cell-cell adhesion, cytoskeletal organization, and cell migration 1. EPHA3 also participates in cardiac development through EFNA1-mediated inhibition of epithelial-to-mesenchymal transition and in neurite guidance during retinotectal mapping 2. In normal lung development, EPHA3 is differentially expressed during alveologenesis and may play critical roles in establishing the alveolar niche 3. EPHA3 variants are associated with white-matter structural connectivity, indicating roles in neurodevelopmental processes 4. Clinically, EPHA3 is highly relevant to oncology as it is frequently overexpressed and/or mutated across multiple malignancies including colorectal, gastric, lung, and brain cancers 5. In gastric cancer, EphA3 overexpression promotes tumor growth and angiogenesis via the STAT3/VEGF pathway 6. EPHA3-targeted chimeric antigen receptor T cells demonstrate potent efficacy against glioblastoma and diffuse midline gliomas in preclinical models, establishing durable anti-tumor immunity 7. Multiple EphA3-targeted therapeutics are currently in development, positioning this receptor as a promising cancer treatment target 85.