Background: Axonal transport of BACE1 and the regulation of BACE1 synaptic localization remain to be fully characterized. Results: Colocalization of BACE1 with synaptophysin was reduced by overexpression of RTN3. This reduction was due to reduced BACE1 axonal transport. Conclusion: Increased interaction of RTN3 with BACE1 in the soma impacts axonal transport of BACE1. Significance: Changes of BACE1 synaptic localization potentially alter synaptic A␤ generation and amyloid deposition.