Ephrin-A2, also known as ELF-1, HEK7-L, LERK-6, and EPLG6, is an approximately 20 kDa member of the Ephrin-A family of GPI-anchored ligands that bind and induce the tyrosine autophosphorylation of Eph receptors. Ephrin-A ligands are structurally related to the extracellular domains of the transmembrane Ephrin-B ligands. Eph-Ephrin interactions are widely involved in the regulation of cell migration, tissue morphogenesis, and cancer progression. Ephrin-A2 preferentially interacts with receptors in the EphA family (1, 2). Mouse Ephrin-A2 is synthesized with a 20 amino acid (aa) signal peptide, a 164 aa mature chain, and a 25 aa C-terminal propeptide which is removed prior to GPI linkage of Ephrin-A2 to the membrane (3, 4). It shares 93% and 100% aa sequence identity with human and rat Ephrin-A2, respectively. Ephrin-A2 is expressed in discrete regions of the developing nervous system and limb buds (4-7). Its distribution complements the pattern of Eph receptor expression, and this plays an important role in tissue morphogenesis (7-9). Ephrin-A2 exerts an axon repulsive signal which is important for the accurate pathfinding of retinal ganglion cell axons to the tectum and hippocampal axons to the lateral septum (8, 10). Its up-regulation in astrocytes at sites of optic nerve damage may prevent re-innervation by retinal ganglion cells (11). Ephrin-A2 is also expressed on neural progenitor cells in the subventricular zone (SVZ). It interacts with EphA7, triggering reverse signaling through Ephrin-A2 and inhibition of progenitor cell proliferation (9). In the developing limbs, Ephrin-A2 regulates cartilage morphogenesis and the projection of motoneuron axons (6, 7, 12).