Ephrin-A4, also known as LERK-4 and EFL-4, is a ligand in the ephrin family that interacts with Eph receptors. All ligands share a conserved extracellular sequence, likely the receptor binding domain, consisting of about 125 amino acids with four invariant cysteines. A-class ligands have a GPI anchor following this sequence. Ephrin-A4 binds EphA2, EphA3, EphA4, EphA5, EphA6, EphA7, and EphB1. Human and mouse Ephrin-A4 extracellular domains share 80% amino acid identity. Membrane-bound or Fc-clustered ligands activate the receptor in vitro, while soluble monomeric ligands bind but do not activate. In vivo, ligands and receptors show reciprocal expression, with nearly all present in developing and adult neural tissue. The Eph/ephrin families also play a role in angiogenesis.