Ebp1, an ErbB3-binding protein, is the human homologue of the cell cycle-regulated mouse protein p38-2G4. Ebp1 was reported to inhibit the proliferation and induce the differentiation of human cancer cells. Its p48 isoform contributes to neuronal differentiation and growth factor specificity. However, the expression and role of Ebp1 in peripheral system lesions and repair are still unknown. Herein, we investigated the spatiotemporal pattern of Ebp1 expression following sciatic nerve crush. After crush, the level of Ebp1 protein was elevated gradually, peaked at day 5, and then declined to the normal at 4 weeks, which was similar to the expression of Oct-6. Furthermore, using double immunofluorescent staining, we found Ebp1 had a colocalization with S100 and Oct-6 in 5-day injured tissues. In vitro, we observed enhanced expression of Ebp1 during the process of cyclic adenosine monophosphate (cAMP)-induced Schwann cells differentiation. Interestingly, Ebp1-depleted SCs did not show significant morphologic change after the treatment of cAMP. Also, we observed a colocalization between Ebp1 and Cyclin D1 and that Ebp1-specific siRNA-transfected SCs had a decreased migration. Taken together, we speculated that Ebp1 was upregulated in the sciatic nerve after crush, which was involved in the differentiation and migration of Schwann cells.