Tph1, the rate-limiting enzyme in serotonin synthesis in certain cell types, is mainly expressed by specialized gut endocrine cells (enterochromaffin cells) and other non-neuronal cell types like adipocytes [3]. Serotonin, synthesized from tryptophan by Tph1, has a wide range of physiological functions, including roles in mood, sleep, anxiety, and gastrointestinal motility regulation, and also in glucose homeostasis and adiposity [3]. Tph1-related research can provide insights into these physiological processes and associated diseases.

In the context of depression, berberine improves depressive symptoms in CUMS-stimulated mice by activating Tph1, promoting tryptophan biotransformation into serotonin and inhibiting the kynurenine metabolism pathway [1]. Regarding suicide behavior, a meta-analysis suggests that the A218C polymorphism of Tph1 gene could be a possible risk factor [2]. In bladder cancer, increasing Tph1 activity inhibits the survival and proliferation of cells via the HIF-1α pathway, indicating Tph1 may be a potential therapeutic target [4]. In pancreatic ductal adenocarcinoma, the overexpression of Tph1 is related to gemcitabine resistance, and knocking down Tph1 can reduce cancer stem cells and reverse resistance [5].

In conclusion, Tph1 is crucial for serotonin synthesis and plays important roles in multiple physiological and disease-related processes. Research on Tph1, especially through genetic models, helps to understand its functions in depression, suicide behavior, bladder cancer, and pancreatic ductal adenocarcinoma, providing potential directions for disease treatment and prevention.