TPH2

Tryptophan Hydroxylase 2 (TPH2) is the rate-limiting enzyme for serotonin (5-hydroxytryptamine, 5-HT) biosynthesis in the central nervous system, distinct from the peripheral isoform TPH1. Its core function is catalyzing the hydroxylation of L-tryptophan to 5-hydroxytryptophan (5-HTP), the first committed step in brain 5-HT production. As 5-HT regulates mood, sleep, appetite, and cognitive processes, TPH2 activity directly modulates CNS serotonin neurotransmission. Common aliases include neuronal tryptophan hydroxylase, reflecting its restricted expression in raphe nuclei serotonergic neurons.
TPH2 is a key component of the serotonin biosynthesis pathway. Genetic variants in TPH2 have been linked to neuropsychiatric disorders such as major depressive disorder, anxiety, bipolar disorder, and autism spectrum disorders, as they disrupt enzyme function or expression, altering brain 5-HT levels. In drug development, TPH2-targeted agents are under investigation: activators aim to boost 5-HT production for depression treatment, while inhibitors are explored for migraine and obsessive-compulsive disorder. Additionally, TPH2 genotypes may predict response to SSRIs, supporting personalized antidepressant therapy strategies.