The group II metabotropic glutamate receptors are known for their involvement in various psychiatric disorders. The mGluR2 in particular is linked with etiology of schizophrenia especially in the context of crosstalk with 5-HT2A. Thus, the mGluR2 has attracted attentions for its potential therapeutic applications. Despite numerous physiological evidences on the actions of mGluR2, its mechanism is still unclear to this day. It is partially due to the lack of understanding in characteristics of mGluR2 homodimer which is its functionally active form. Therefore, the characterization of dimeric interaction serves as a foundation to advanced understanding of the role of mGluR2. On that note, the role of the conserved cysteine residue (C121) in the ligand binding domain of mGluR2 has been evaluated in this study as they are known to play a critical part in homodimer formation. Collectively, C121 has been shown to affect the dimerization, subcellular localization, and pharmacokinetics of mGluR2. Lastly, the effect of mGluR2 on mouse behavior was examined in a partial effort to elucidate its role in crosstalk with 5-HT2A.