Ephrin-A5 prevents axon bundling in cocultures of cortical neurons with astrocytes, a model of late stage nervous system development and differentiation. The EPH and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, particularly in the nervous system. EPH receptors typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin ligands and receptors have been named by the Eph Nomenclature Committee. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B class, which are transmembrane proteins.