EPHB6 encodes a kinase-defective receptor tyrosine kinase that functions as a molecular switch in signal transduction pathways 1. Unlike conventional Eph receptors, EPHB6 lacks kinase activity but acts as a scaffold protein that modulates Eph receptor cluster signaling by recruiting adaptor proteins 1. EPHB6 demonstrates significant tumor suppressor activity across multiple cancer types. In neuroblastoma, high EPHB6 expression is associated with favorable patient outcomes and low tumor stages, with transfection studies showing direct inhibition of cell clonogenicity and tumorigenicity 2. In breast cancer, EPHB6 loss correlates with invasive phenotypes, and restoration reduces invasiveness by modulating matrix metalloproteinase expression 3. Similarly, in colorectal cancer, EPHB6 loss promotes metastatic spread, with significantly lower expression observed in lymph node metastases compared to primary tumors 4. EPHB6 also regulates neuronal function and gut-brain axis communication, with deficiency causing autism-like behaviors through disrupted gut microbiota and vitamin B6/dopamine metabolism 5. The receptor's unique structural organization allows it to function through ligand-binding domain interactions and requires co-receptors for signaling due to its kinase-inactive nature 6.