Ligand Recognition and Function of TAARs

ABSTRACT Trace amine‐associated receptors (TAARs) represent an evolutionarily ancient family of G protein‐coupled receptors that function in both the periphery and central nervous systems. Originating from ancestral serotonin receptors through vertebrate‐specific gene duplications, TAARs have diversified into a specialized olfactory receptor subfamily tuned to detect ethologically relevant amines, as well as TAAR1, a special member that detects trace amines to modulate monoaminergic brain circuits. The olfactory TAARs mediate hardwired responses to predator odors and social cues, whereas the nonolfactory TAAR1 has emerged as a potential therapeutic target for neuropsychiatric disorders. By integrating the evolutionary history, gene expression mechanisms, ligand recognition, and functional insights of TAARs, this review highlights how TAARs operate as polymodal sensors that translate chemical information into behavioral and physiological responses—offering crucial perspectives on the development of distinct neural circuits and targeted therapeutics.