EFNB2 (ephrin B2) is a membrane-bound ligand that functions in bidirectional signaling through EPH receptor tyrosine kinases, playing critical roles in vascular development, immune regulation, and tissue homeostasis. EFNB2 promotes angiogenesis and lymphangiogenesis through activation of downstream signaling pathways, including the CDK5/ISL1 pathway that enhances VEGFR3 transcription 1. In vascular smooth muscle cells, EFNB2 regulates contractility through both forward signaling to EPH receptors and reverse signaling, with EPHB4 serving as a critical receptor for forward signaling 2. The protein is essential for proper blood pressure regulation, as smooth muscle-specific EFNB2 deletion reduces blood pressure in male mice, and human genetic variants in EFNB2 are associated with hypertension risk 2. EFNB2 also mediates osteoblast-osteoclast communication through EFNB2-EPHB4 interactions, regulating bone remodeling 3. In immune function, T cell expression of EFNB2 is crucial for pathogenic antibody production and T cell migration in autoimmune conditions like rheumatoid arthritis 4. Additionally, EFNB2 contributes to cancer progression, as elevated levels facilitate tumor development through mTORC1 signaling pathways 5. The protein's diverse functions span cardiovascular physiology, immune responses, bone homeostasis, and pathological processes including cancer and metabolic disorders.