TAAR5 Pharmacology

Trace amine-associated receptor 5 (TAAR5) belongs to the TAAR family of G protein-coupled receptors, which detect trace amines, small molecules structurally related to monoamine neurotransmitters but present at much lower concentrations in vertebrate and invertebrate tissues. In both humans and rodents, TAAR5 is predominantly expressed in the olfactory epithelium, with lower expression also observed in the central nervous system. As an odorant receptor, TAAR5 is the principal mediator of trimethylamine sensing, an odor that is aversive in humans but has a crucial social function in mice. Accumulating evidence indicates that TAAR5 modulates serotonergic and dopaminergic neurotransmission within the central nervous system and is involved in affective, cognitive, and sensorimotor behaviors. More recently, TAAR5 has been implicated in a microbiota-derived trimethylamine signaling axis associated with circadian regulation. This chapter reviews the key studies that have shaped the current understanding of TAAR5, from its discovery to its involvement in complex central nervous system and behavioral processes.