Although NHE1 inhibitors are known to effectively retard cell proliferation of different malignant tumor cells [8–11], we have shown that NHE5 knockdown by shRNA markedly diminishes the proliferation and invasion of C6 glioma cells, and demonstrate that NHE5 knockdown has a significantly different effect on tumor growth and invasion in mouse xenografts compared to the impact caused by NHE1 knockdown. The gene discussed is SLC9A5; the disease is glioma.