**2. Regulation of EAAC1 function by addicsin**

The mechanisms by which addicsin regulates EAAC1 activity have not been definitively established. However, the discovery of addicsin/GTRAP3-18 has contributed greatly to our understanding of EAAC1 function. Recent evidence demonstrates two major mechanisms of addicsin-mediated regulation of EAAC1 activity. One regulatory pathway is dependent on the dynamic competition for free addicsin molecules by other addicsin molecules to form the homocomplex and by Arl6ip1 to form a heterocomplex. This addicsin–Arl6ip1 complex sequesters addicsin molecules and blocks the interaction of addicsin with EAAC1 in the plasma membrane, thereby reducing the inhibitory effect of addicsin on EAAC1-mediated glutamate uptake (Akiduki & Ikemoto, 2008; Lin et al., 2001) (Fig. 3). Second, addicsin functions as a negative regulator of EAAC1 trafficking through the ER and inhibits the cell surface expression of EAAC1 (Liu et al., 2008; Ruggiero et al., 2008). In this section, we discuss these two mechanisms in detail.
