The Wilms tumor suppressor gene WT1 is essential for early urogenital development: homozygous mutations in WT1 result in embryonic lethality due to a failure in the development of kidneys and gonads. In the adult kidney, WT1 expression is limited to the glomerular podocytes. Several human nephrotic diseases arise from mutations of the WT1 gene, including mutations that affect its zinc-fingers and alternative splicing of +/- KTS isoforms. These include WAGR (for Wilms tumor, aniridia, genitourinary anomalies, and mental retardation), and Frasier and Denys-Drash syndromes. Recent advances including the development of transgenic mouse models and conditionally immortalized podocyte cell lines are beginning to shed light on WT1's crucial role in podocyte function.