Glutamate receptor delta 2 subunit (GluR delta 2) is selectively expressed in cerebellar Purkinje cells and is specifically targeted to parallel fiber synapses, where GluR delta 2 plays important roles in synaptic plasticity, motor learning and synapse formation. Here, we investigated the mechanism of GluR delta 2 sorting using MDCK epithelial cells. Immunocytochemical analysis of subcellular localization showed that GluR delta 2 expressed in MDCK cells was predominantly distributed in the plasma membrane. By examining the subcellular localization of GluR delta 2 mutants with various deletions in the carboxyl-terminal cytoplasmic region, we identified J segment adjacent to transmembrane segment M4 as a key region for the efficient targeting of GluR delta 2 to the plasma membrane. On the other hand, the carboxyl terminus of GluR delta 2 essential for interaction with PDZ domain proteins was dispensable for the plasma membrane localization. Our results suggest that the juxtamembrane segment and the PDZ domain target site at the carboxyl terminus of GluR delta 2 play differential roles in plasma membrane targeting, synapse localization and signal transduction.