Wilson Disease Protein (WNDP) is a copper-transporting ATPase, the high physiological importance of which is underlined by its involvement in Wilson Disease (WD), an inherited disorder with severe hepatic and neurological symptoms caused by accumulation of copper in liver and brain. Despite recent progress in expression and functional characterization of WNDP, many details about the molecular mechanism, the determinants of copper-dependent regulation, and trafficking within cells are still poorly understood, raising the need for new expression systems and independent experimental approaches. Here, epitope insertion, expression in Xenopus oocytes, and chemiluminescence measurements have been used to evaluate topological features of WNDP and to quantify its plasma membrane localization. Expression of WNDP at the plasma membrane is additionally verified by electron microscopy of freeze-fractured oocyte preparations. The developed surface detection assay is used to quantify the effects of protein sequence modifications on plasma membrane localization of WNDP.The expression of WNDP in Xenopus oocytes opens a novel route to investigate the effects of Wilson Disease sequence variants on subcellular distribution of this important enzyme.