Collectively, our findings uncover a previously unrecognized FXYD1-MAEA-DDX5 axis that inhibits Wnt/β-catenin signaling through a non-canonical ubiquitin-proteasome pathway, establishing FXYD1 as a tumor suppressor and potential prognostic biomarker and therapeutic target in breast cancer. This evidence concerns the gene FXYD1 and breast cancer.