EPHA6 is a receptor tyrosine kinase that binds GPI-anchored ephrin-A ligands on adjacent cells, initiating contact-dependent bidirectional signaling involved in axon guidance and cell-cell communication. EPHA6 exhibits context-dependent roles in cancer: in prostate cancer, EPHA6 is consistently overexpressed in metastatic cells and promotes invasion, angiogenesis, and metastasis, correlating with vascular invasion, neural invasion, PSA levels, and TNM staging 1. Conversely, in glioblastoma, high EPHA6 expression correlates with better prognosis, and EPHA6 sensitizes glioma-initiating cells to BMP-2-induced apoptosis through interaction with the BMP type I receptor ALK-2 2. In uveal melanoma, high EPHA6 nuclear expression associates with older age at diagnosis and absence of retinal detachment 3. During retinal development, the transcription factor HMX1 negatively regulates EPHA6 expression to modulate axon guidance 4. Circulating long noncoding RNA LNC-EPHA6 associates with vascular injury and acute kidney transplant rejection, suggesting EPHA6-related mechanisms influence vascular integrity 5. These findings establish EPHA6 as a multifaceted regulator with therapeutic potential in cancer and transplantation contexts.