EPHB1 encodes a receptor tyrosine kinase that binds ephrin-B ligands and mediates bidirectional cell signaling crucial for multiple biological processes. In cancer contexts, EPHB1 functions as a tumor suppressor, particularly in colorectal cancer where somatic mutations impair its kinase activity and reduce cell compartmentalization 12. These cancer-associated mutations compromise EPHB1's ability to suppress cell migration and inhibit STAT3/ERK signaling pathways 2. Conversely, EPHB1 can promote tumor progression in other contexts, such as facilitating pancreatic cancer liver metastasis through EPHB1-EFNB1 reverse signaling that activates platelets and enhances 5-HT release 3. In prostate adenocarcinoma, EPHB1 activates the GSK3B-SMAD3 pathway, promoting antiapoptotic features and macrophage M2 polarization 4. EPHB1 also contributes to retinal pathology, where increased expression in diabetic conditions leads to inflammatory responses in Müller cells and enhanced retinal damage during ischemia/reperfusion 5. In hematologic malignancies, IRF4-C99R mutations upregulate EPHB1 expression, influencing thymic tropism in primary mediastinal large B-cell lymphoma 6. The receptor's dual roles highlight its context-dependent functions in both tumor suppression and progression.