Tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of catecholamines, is a key protein involved in the pathogenesis of neurodegenerative diseases such as Parkinson's disease. Elucidation of the mechanisms regulating the synthesis, degradation, and activity of TH should be a first target in order to understand the role of this enzyme in pathogenesis. Recently, several reports suggest that the ubiquitin-proteasome pathway is a prerequisite for the degradation of TH and that the N-terminal part of TH plays a critical role in the degradation. In this report, we propose the mechanism by which the N-terminal part of TH regulates the degradation of this enzyme. Moreover, we integrate our findings with recent progress in other areas of TH regulation.