GDNFR.alpha., GDNFR.alpha. extracellular domain (ECD), GDNFR.alpha. variants, chimeric GDNFR.alpha. (e.g., GDNFR.alpha. immunoadhesin), and antibodies which bind thereto (including agonist and neutralizing antibodies) are disclosed. Various uses for these molecules are described, including methods to modulate cell activity and survival by response to GDNFR.alpha.-ligands, for example GDNF, by providing GDNFR.alpha. to the cell. Also provided are methods for using GDNFR.alpha., GDNF, or agonists thereof, separately or in complex, to treat kidney diseases.