The study identifies a family of 15 G protein-coupled receptors (GPCRs) from human and rodent tissues, which are activated by trace amines such as tyramine, β-phenylethylamine, tryptamine, and octopamine. These receptors, along with the orphan receptor PNR, form a subfamily distinct from classical biogenic amine receptors but related to them. The identification of these receptors supports the role of trace amines as neurotransmitters in vertebrates and suggests potential therapeutic applications. Three of the four human receptors are expressed in the amygdala, which may link trace amine receptors to affective disorders. The study also reports the localization of TA1 mRNA in various tissues and its chromosomal localization on chromosome 6q23.2, close to a schizophrenia susceptibility locus. The findings highlight the physiological roles of trace amines and their receptors in higher species and their potential in disease treatment.The study identifies a family of 15 G protein-coupled receptors (GPCRs) from human and rodent tissues, which are activated by trace amines such as tyramine, β-phenylethylamine, tryptamine, and octopamine. These receptors, along with the orphan receptor PNR, form a subfamily distinct from classical biogenic amine receptors but related to them. The identification of these receptors supports the role of trace amines as neurotransmitters in vertebrates and suggests potential therapeutic applications. Three of the four human receptors are expressed in the amygdala, which may link trace amine receptors to affective disorders. The study also reports the localization of TA1 mRNA in various tissues and its chromosomal localization on chromosome 6q23.2, close to a schizophrenia susceptibility locus. The findings highlight the physiological roles of trace amines and their receptors in higher species and their potential in disease treatment.