Addicsin is a negative modulator of neural glutamate transporter EAAC1. It associates with Arl6ip1, an ER localized anti-apoptotic factor involved in onset of hereditary spastic paraplegia. Addicsin indirectly promotes EAAC1-mediated glutamate transport activity by increasing Addicsin-Arl6ip1 (AA) complex formation. However, this physiological significance and molecular mechanism remain largely unknown. Here, to clarify these questions, we examined the relationship between the dynamics of AA complex and oxidative stress sensitivity. Both Arl6ip1/Addicsin mRNA expression ratio and H2O2-induced cell toxicity showed a very high correlation. Moreover, H2O2 -oxidative stress sensitivity in C6BU-1 cells was drastically increased in overexpression of Arl6ip1 and AddicsinY110AL112A lacking binding ability for Arl6ip1. Immunocytochemical analysis showed that addicsin co-localized with Arl6ip1, whereas translocated to plasma membrane by 100 µM H2O2 exposure. These results support that AA complex dissociationinduced by addicsin translocation from ER to plasma membrane may be an important physiological phenomenon to regulate oxidative stress sensitivity in neuronal cells. I would like to discuss Arl6ip1-depedndent apoptosis signals.