We report that 1) Fyn was highly expressed in nigral DAergic neurons; 2) suppression of Fyn by tyrosine kinase inhibitor or RNAi-mediated knockdown (KD) attenuated PKCδ Y311 phosphorylation and its proteolytic activation as well as DAergic neuronal apoptosis; and 3) Fyn KO mice were significantly protected from MPTP-induced DAergic degeneration and locomotor deficits, thereby providing overall credence to the premise that Fyn could serve as a novel pharmacological target of PD. This evidence concerns the gene FYN and Parkinson disease.