Mutant mice lacking the integrin α8 subunit exhibit variable defects in kidney development with most mutants missing both kidneys. Several lines of evidence indicate that the known extracellular matrix ligands for integrin α8β1 are either dispensable for or not involved in α8β1 signaling during kidney development. This suggests the presence of an unknown ligand. A novel α8β1 ligand, nephronectin, has now been identified. Nephronectin is a new extracellular matrix protein associated with the Wolffian duct and the ureteric bud, epithelial structures with well-defined roles in kidney development.