EPHBs are involved in spine synapse formation and also for the recruitment and clustering of glutamate receptors to synapses. At the time of synaptogenesis, EPHBs are localized to the postsynaptic region of excitatory synapses. These postsynaptic EPHBs, upon activation by presynaptic ephrinBs (EFNBs), directly interact with ionotropic glutamate receptor, NR1 and NR2B (NMDAR1and 2B aka GRIN1and 2B). The interaction between EPHB and NMDARs is mediated by the extracellular domains of these two proteins. This interaction promotes clustering of NMDARs at synaptic locations and leads to the formation of functional presynaptic release sites. Activated EPHBs function as tyrosine kinases and may also indirectly potentiate NMDAR-mediated calcium influx (Dalva et al. 2000, Takasu et al. 2002).