Transient receptor potential (TRP) channels are multifunctional signalling molecules with many roles in sensory perception and cellular physiology. Therefore, it is not surprising that TRP channels have been implicated in numerous diseases, including hereditary disorders caused by defects in genes encoding TRP channels (TRP channelopathies). Most TRP channels are located at the cell surface, which makes them generally accessible drug targets. Early drug discovery efforts to target TRP channels focused on pain, but as our knowledge of TRP channels and their role in health and disease has grown, these efforts have expanded into new clinical indications, ranging from respiratory disorders through neurological and psychiatric diseases to diabetes and cancer. In this Review, we discuss recent findings in TRP channel structural biology that can affect both drug development and clinical indications. We also discuss the clinical promise of novel TRP channel modulators, aimed at both established and emerging targets. Last, we address the challenges that these compounds may face in clinical practice, including the need for carefully targeted approaches to minimize potential side-effects due to the multifunctional roles of TRP channels.

瞬时受体电位 (TRP) 通道是多功能信号分子，在感觉知觉和细胞生理学中具有多种作用。因此，毫不奇怪，TRP 通道与许多疾病有关，包括由编码 TRP 通道的基因缺陷引起的遗传性疾病（TRP 通道病）。大多数 TRP 通道位于细胞表面，这使得它们通常可接近药物靶点。针对 TRP 通道的早期药物发现工作主要集中在疼痛上，但随着我们对 TRP 通道及其在健康和疾病中作用的了解不断增加，这些努力已扩展到新的临床适应症，从呼吸系统疾病到神经和精神疾病再到糖尿病和癌症。在这篇评论中，我们讨论了 TRP 通道结构生物学的最新发现，这些发现可以影响药物开发和临床适应症。我们还讨论了针对既定目标和新兴目标的新型 TRP 通道调节剂的临床前景。最后，我们解决了这些化合物在临床实践中可能面临的挑战，包括需要精心靶向的方法，以尽量减少由于 TRP 通道的多功能作用而导致的潜在副作用。