Background:The LZTS2 is a novel -catenin-interacting protein, and its role in development and tumorigenesis is unknown. Results: Lzts2 KO mice show severe kidney and urinary tract developmental defects, including renal/ureteral duplication, hydroureter, and hydronephrosis. Conclusion: LZTS2 plays a critical role in kidney and urinary tract development. Significance: A novel mechanism by which LZTS2 regulates -catenin mediated nephrogenesis is implicated.