T-lymphoma invasion and metastasis-inducing protein 1 (TIAM1) is a GEF exhibiting highest specificity for RAC1 and is critically involved in EPH/ephrin (EFN)-mediated neurite outgrowth and dendritic spine development (Tanaka et al. 2004, Tolias et al. 2007). TIAM1 has a role in regulating the endocytosis of EPHA receptors, by regulating the RAC1 signaling downstream of the EPHA8 receptor. Yoo and his colleagues found that TIAM1, a RAC-specific guanine nucleotide exchange factor, co-immunoprecipitates with EPHA8 in response to EFNA5 stimulation. TIAM1 associates with EPHA8 in the juxtamembrane (JM) region. Deletion of the JM region or down-regulation of TIAM1 expression compromises EPHA8:EFNA5 endocytosis (Yoo et al. 2010).