After acute kidney injury (AKI), surviving cells within the filtering nephron proliferate and repair. We screened injured mouse kidneys to identify regulatory genes linked to this repair process identifying a member of the Sox family, Sox9, as new factor in the injury/repair response. Sox9 encodes a regulatory factor known to control gene activity in other cell types. Mapping the relationship between Sox9 activation and nephron repair showed Sox9+ cells are the main cell source for renal repair and Sox9 is itself critical for a normal repair process. Further study of Sox9 action is predicted to give important insights into the mechanisms that switch surviving cells from functional to reparative mode in the injured kidney.