α-Synuclein (α-Syn) is implicated in several neurodegenerative disorders, including Parkinson’s disease, known collectively as the synucleinopathies. α-Syn is known to be secreted from the cells and may contribute to the progression of the disease. Although extracellular α-Syn is shown to impair platelet-derived growth factor-induced chemotaxis, molecular mechanism of α-Syn-induced motility failure remains elusive. Here we have aimed at phospholipase D (PLD) as a potential target for α-Syn and examined the involvement of this enzyme in α-Syn action. Indeed, extracellular α-Syn caused inhibition of agonist-induced PLD activation. However, inhibition of hydrolytic activity of PLD by 1-butanol treatment showed little or no effect on agonist-induced chemotaxis. These results suggest that some signaling pathways other than PLD may be involved in α-Syn-induced inhibition of chemotaxis