EPHA7 (EPH receptor A7) is a receptor tyrosine kinase that mediates contact-dependent bidirectional cell signaling through interaction with GPI-anchored ephrin ligands, particularly EFNA5 1. In normal physiology, EPHA7 regulates brain development through forward signaling that activates ERK pathway components (MAP2K1, MAP2K2, MAPK1, MAPK3) and controls axon guidance, cell-cell adhesion, and neuronal apoptosis [UniProt]. EPHA7 exhibits dual roles in tumorigenesis: it functions as both a tumor suppressor and promoter depending on cancer context 1. In prostate cancer, EphA7 undergoes promoter hypermethylation in 41.7% of cases, resulting in transcriptional silencing and loss of protein expression correlated with higher Gleason scores 2. Similarly, aberrant EphA7 methylation occurs in cervical cancer; targeted demethylation via dCas9-Tet1 restores expression and inhibits proliferation and invasion through PI3K/AKT pathway suppression while enhancing chemotherapy sensitivity 3. Conversely, EPHA7 upregulation serves as a diagnostic biomarker for colorectal cancer and gastric cancer recurrence [PMID:32421395; 45]. In hematopoiesis, EphA7 forward signaling promotes hematopoietic stem/progenitor cell maintenance and migration via Rac1 activation 5. EPHA7 mutations are also identified in small-cell lung cancer 6 and follicular lymphoma 7, establishing it as a clinically relevant target for cancer diagnostics and therapeutics.