EFNB3 encodes ephrin-B3, a transmembrane ligand protein that plays critical roles in neural development and pathological processes. (a) Primary function: EFNB3 functions as a ligand for EPH family receptor tyrosine kinases, particularly mediating axon guidance and spinal midline barrier formation during neurodevelopment 1. It participates in cell-cell signaling within the nervous system and regulates synaptic development 2. (b) Mechanism: EFNB3 operates through EPH-ephrin signaling pathways, with recent evidence showing it controls astrocyte responses via EphB3 receptors in microglia-astrocyte interactions 2. The protein also regulates intestinal barrier function through ITGB4/AKT signaling and inflammatory responses via Gremlin-1/NF-κB pathways 3. (c) Disease relevance: EFNB3 expression patterns correlate with neuroblastoma prognosis, where high expression associates with favorable outcomes and low tumor stages 45. Loss-of-function variants cause congenital mirror movement disorders, as demonstrated in Weimaraner dogs with frameshift mutations 1. The gene also influences colitis severity and colorectal cancer development 3. (d) Clinical significance: EFNB3 serves as a prognostic biomarker in neuroblastoma and represents a potential therapeutic target for inflammatory bowel disease and associated cancers.