The discovery in 2001 of a G protein-coupled receptor family, subsequently termed trace amine-associated receptors (TAAR), triggered a resurgence of interest in so-called trace amines. Initial optimism quickly faded, however, as the TAAR family presented a series of challenges preventing the use of standard medicinal chemistry and pharmacology technologies. Consequently the development of basic tools for probing TAAR and translating findings from model systems to humans has been problematic. Despite these challenges the last 5 years have seen considerable advances, in particular with respect to TAAR1, which appears to function as an endogenous rheostat, maintaining central neurotransmission within defined physiological limits, in part through receptor heterodimerization yielding biased signaling outputs. Regulation of the dopaminergic system is particularly well understood and clinical testing of TAAR1 directed ligands for schizophrenia and psychiatric disorders have begun. In addition, pre-clinical animal models have identified TAAR1 as a novel target for drug addiction and metabolic disorders. Growing evidence also suggests a role for TAARs in regulating immune function. This review critically discusses the current state of TAAR research, highlighting recent developments and focussing on human TAARs, their functions, and clinical implications. Current gaps in knowledge are identified, along with the research reagents and translational tools still required for continued advancement of the field. Through this, a picture emerges of an exciting field on the cusp of significant developments, with the potential to identify new therapeutic leads for some of the major unmet medical needs in the areas of neuropsychiatry and metabolic disorders.

2001年，一个G蛋白偶联受体家族（后来称为痕量胺相关受体（TAAR））的发现引发了人们对所谓的痕量胺的兴趣再次兴起。然而，最初的乐观情绪很快消失了，因为TAAR家族提出了一系列挑战，阻碍了标准药物化学和药理学技术的使用。因此，开发用于探测TAAR并将结果从模型系统转换为人类的基本工具的开发一直存在问题。尽管存在这些挑战，最近5年仍取得了长足的进步，尤其是TAAR1，它似乎起内源性变阻剂的作用，部分通过受体异二聚化产生偏向的信号输出，从而将中枢神经传递保持在规定的生理限度内。对多巴胺能系统的调节特别了解，并且针对精神分裂症和精神疾病的TAAR1定向配体的临床测试已经开始。此外，临床前动物模型已经将TAAR1鉴定为药物成瘾和代谢紊乱的新型靶标。越来越多的证据还表明TAAR在调节免疫功能中的作用。这篇评论批判性地讨论了TAAR研究的现状，强调了最近的发展，并着重于人类TAAR，其功能和临床意义。确定了当前的知识差距，以及该领域的持续发展仍需要的研究试剂和翻译工具。这样一来，在重大发展的顶峰就出现了一个令人兴奋的领域，