Ephexin1/NGEF (Neuronal guanine nucleotide exchange factor) is a member of the Dbl family of guanine nucleotide exchange factors (GEFs) for Rho GTPases, which interacts with cytoplasmic domain of EPHAs. NGEF is highly expressed in the CNS during development and is enriched in neuronal growth cones. NGEF binds to the kinase domain of EPHA through its Dbl homology (DH)-pleckstrin-homology (PH) domains and this binding does not require activation of the receptor. EPHA activation by ephrinA ligands increases the catalytic activity of ephexin1 resulting in enhanced RHOA activation in cortical neurons (Noren & Pasquale 2004, Shamah et al. 2001). Ephrin-A1 also induces the dispersal of acetylcholine receptors clusters at the neuromuscular junction through the activation of NGEF and RhoA (Shi et al., 2010). NGEF is involved in both axonal growth,growth cone collapse, dendritic spine elimination and stabilization of the neuromuscular junction. In the absence of ephrin stimulation, NGEF promotes actin polymerization and axonal growth by stimulating RHOA, RAC1 and CDC42. Whereas in the presence of ephrin stimulation, NGEF induces growth cone collapse by activating RHOA, but not RAC1 and CDC42 (Shamah et al. 2001, Sahin et al. 2005).