EPHA5 (EPH receptor A5) is a receptor tyrosine kinase that plays critical roles in neuronal development, immune function, and cancer biology. In hematopoiesis, EPHA5 is specifically expressed on primitive hematopoietic stem and progenitor cells (CD34+CD38-) where it binds ephrinA5 ligand on bone marrow stromal cells, promoting cell maintenance, migration, and adhesion through Rac1 activation 1. In immune function, EPHA5 regulates antifungal responses by phosphorylating both EPHB2 and Dectin-1 receptors, facilitating Syk activation and downstream signaling pathways essential for combating invasive fungal infections 2. In cancer, EPHA5 exhibits context-dependent roles: it functions as a tumor suppressor in prostate cancer where promoter hypermethylation leads to downregulation associated with higher Gleason scores and advanced staging 3, while in lung adenocarcinoma, EPHA5 overexpression correlates with lymph node metastasis, poor differentiation, and EGFR mutations 4. The receptor also shows therapeutic potential, as EPHA5-targeted antibody-drug conjugates demonstrate efficacy against multiple solid tumors in preclinical studies 5. Additionally, EPHA5 methylation in peripheral blood leukocytes serves as a biomarker for gastric cancer risk 6.