Midbrain dopamine (DA) neurons possess complex branching structures and demand significant metabolic resources . This intricate architecture makes these neuron susceptible, emphasizing the role of intracellular trafficking in the early development of Parkinson's disease (PD). Recent genetic screenings in Asian and European populations have unveiled SV2C (synaptic vesicle glycoprotein C) as a newly discovered gene associated with PD. Specifically, the D543N mutation has been linked to PD. It is hypothesized that this mutation introduces a new glycosylation site in the SV2C protein, underscoring the significance of glycosylation and SV2C in PD associations. Since glycosylation plays a crucial role in the proper trafficking and synaptic targeting of transmembrane proteins, our study will initially focus on identifying the novel role of glycosylation. This will involve mutating all five native glycosylation sites in SV2C, rendering it non-glycosylated (NQ SV2C). First, we show the loss of glycosylation affects the synaptic targeting and secretory pathway of SV2C in both cell line and neuronal model. Additionally, we confirmed D543N mutation results in gain of glycosylation through biochemical analysis and mass spectrometry. Such additional glycan does not imposed obvious change in proteins trafficking, but slightly accelerates the ER-Golgi early trafficking. Overall, our study demonstrates the novel role glycosylation in facilitating the proper trafficking of SV2C in a loss of function study. Conversely, our findings reveal that the gain of glycosylation accelerates trafficking during early vesicle biogenesis, potentially conferring a compensatory/protective effect against DA deficiency in PD patients.