EAAT4 (SLC1A6) is a Purkinje-Cell specific postsynaptic excitatory amino acid transporter that plays a major role in clearing synaptic glutamate. EAAT4 abundance and function is known to be modulated by the serum and glucocorticoid inducible kinase (SGK) 1 but the precise mechanism of kinase action has not been defined yet. The present work aimed to identify the molecular mechanism of EAAT4 modulation by the kinase. EAAT4 bears two putative SGK1 consensus sites (at Thr40 and Thr504) that are conserved among species. Expression studies in Xenopus oocytes demonstrated that EAAT4-mediated glutamate uptake and cell surface abundance are enhanced by SGK1. Disruption of the SGK1 phosphorylation site at threonine 40 or of both phosphorylation sites abrogated the effect of SGK1 on transporter function and expression. SGK1 modulates several transport proteins via inhibition of the ubiquitin ligase Nedd4-2. Coexpression of Nedd4-2 inhibited wild-type EAAT4 but not the T40AT504AEAAT4 mutant. Besides, RNA interference- mediated reduction of endogenous Nedd4-2 (xNedd4-2) expression increased the activity of the transporter. In conclusion, maximal glutamate transport stimulation by SGK1 is accomplished by EAAT4 phosphorylation and to a lesser extent by inhibition of intrinsic Nedd4-2.