TH (tyrosine hydroxylase) is an enzyme that converts L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA), a dopamine precursor. It is the rate-limiting enzyme in the synthesis of catecholamines and plays a key role in the physiology of adrenergic neurons. TH is encoded by four distinct mRNAs produced by alternative splicing of a single primary transcript, and expression of the mRNAs varies in different parts of the nervous system. Mutations in TH are the cause of autosomal recessive Segawa syndrome and are thought to be involved in Parkinson’s disease and schizophrenia. TH deficiency leads to dopa-nonresponsive dystonia and progressive encephalopathy via an impaired ability to synthesize epinephrine, norepinephrine and dopamine. In immunohistochemistry of normal tissue, TH has cytoplasmic positivity in the adrenal medulla, in peripheral sympathetic nerve fibers, and in the caudate nucleus in the brain. References: Nature Structural Biology. 1997. 4 (7): 578–85, PMID 9228951; CNS Neurol Disord Drug Targets. 2012 Jun 1;11(4):395-409, PMID: 22483313; Arch Biochem Biophys. 2011 Apr 1;508(1):1-12, PMID: 21176768; Ann Neurol. 2003;54 Suppl 6:S56-65, PMID: 12891655