Recent studies suggest members of the Degenerin/Epithelial Na⁺ Channel/Acid Sensing Ion Channel (DEG/ENaC/ASIC) protein family play an important role in Vascular Smooth Muscle Cell (VSMC) migration. In a previous investigation, we found suppression of a certain DEG/ENaC/ASIC member, ASIC2, increased VSMC chemotactic migration, raising the possibility that ASIC2 may play an inhibitory role. Since ASIC2 protein was retained in the cytoplasm, we reasoned increasing surface expression of ASIC2 might unmask the inhibitory role of ASIC2 in VSMC migration, so we could test the hypothesis that ASIC2 inhibits VSMC migration. Therefore, we used the chemical chaperone glycerol to enhance ASIC2 expression. Glycerol 1) increased cytoplasm ASIC2 expression, 2) permitted detection of ASIC2 at the cell surface, and 3) inhibited PDGF-bb mediated VSMC migration. Furthermore, ASIC2 silencing completely abolished the inhibitory effect of glycerol on migration, suggesting upregulation of ASIC2 is responsible for glycerol-induced inhibition of VSMC migration. Since other investigators have shown glycerol regulates ENaC/ASIC via interactions with a certain heat shock protein, Hsc70, we wanted to determine the importance of Hsc70 on ASIC2 expression in VSMCs. We found Hsc70 silencing increases ASIC2 cell surface expression and inhibits VSMC migration, which is abolished by co-silencing ASIC2. These data demonstrate Hsc70 inhibits ASIC2 expression and when the inhibitory effect of Hsc70 is removed, ASIC2 expression increases, resulting in reduced VSMC migration. Since VSMC migration contributes to vasculogenesis and remodeling following vascular injury, our findings raise the possibility that ASIC2-Hsc70 interactions may play a role in these processes.