This study establishes a key role for the developmental transcription factors Lmx1a/b in the maintenance of midbrain dopamine neurons. The authors show that postmitotic ablation of Lmx1b in mice leads to cellular and functional abnormalities resembling Parkinson's disease, most notably in a dysfunction in the autophagic-lysosomal pathway that results in abnormal dopaminergic synaptic connections and neuronal degeneration.