Vol. 7, Issue 2, Part F (2025)

The EPH receptor tyrosine kinases and their membrane-bound ephrin ligands constitute a pivotal cell communication system orchestrating a multitude of physiological processes, including embryonic development, tissue patterning, neural plasticity, and immune response. Their unique ability to facilitate bidirectional signaling allows them to modulate the behavior of both the receptor-expressing and ligand-expressing cells upon contact. This comprehensive review delineates the molecular architecture and signaling mechanisms of the Eph/ephrin system, highlighting its critical roles in neural development, vascular patterning, bone remodeling, and glucose homeostasis. We further explore the system's dual role in pathology, particularly in cancer progression, angiogenesis, and drug resistance, where its dysregulation can either promote or suppress tumorigenicity in a context-dependent manner. Finally, we discuss emerging therapeutic strategies including CRISPR/Cas9 gene editing, nanoparticle-based drug delivery, and artificial intelligence-driven drug designthat target the Eph/ephrin axis, underscoring its significant potential for pioneering next-generation precision medicine interventions.