转瞬即逝的受体电位（TRP）通道分为六个亚家族（-A、-V、-P、-C、-M、-ML、-N和-Y），是重要的膜传感器和介导多种刺激（包括pH、光、机械力、温度、疼痛、味觉和嗅觉）的介质。哺乳动物TRP超家族有28个成员，具有类似的膜拓扑结构，包括六个跨膜螺旋（S1-S6）和胞浆N-/C-末端。 TRP通道功能或表达异常与癌症、骨发育不良、免疫缺陷以及心脏、肾脏和神经系统疾病有关。大多数TRP成员共享常见的功能调控器，如磷脂PIP2、2-氨基乙氧二苯硼（2-APB）和大麻素，而其他结合物则更具特异性，例如烯丙基异硫氰酸酯（TRPA1）、辣椒素（TRPV1）、薄荷醇（TRPM8）、ADP核糖（TRPM2）和ML-SA1（TRPML1）等。TRP通道的开放和调节机制仍不清楚。最近，低温电子显微镜的进展为19种不同的TRP通道提供了结构洞见，所有这些结构都显示C-末端与N-末端和细胞内的S4-S5连接器相互靠近。进一步的研究发现，TRPV、-P、-C和-M成员这些区域中的一些高度保守的残基介导着这些区域之间的功能关键的分子内相互作用（即在一个亚基内）。本综述概述了TRP通道的分子内相互作用对通道功能的影响，PIP2（和其他结合物）和TRP分子内相互作用之间的功能相互作用，以及配体引起的分子内相互作用调节与疾病的相关性。 ©2022年。作者（s）独家授权给Springer Nature Switzerland AG。

The transient receptor potential (TRP) channels, classified into six (-A, -V, -P, -C, -M, -ML, -N and -Y) subfamilies, are important membrane sensors and mediators of diverse stimuli including pH, light, mechano-force, temperature, pain, taste, and smell. The mammalian TRP superfamily of 28 members share similar membrane topology with six membrane-spanning helices (S1-S6) and cytosolic N-/C-terminus. Abnormal function or expression of TRP channels is associated with cancer, skeletal dysplasia, immunodeficiency, and cardiac, renal, and neuronal diseases. The majority of TRP members share common functional regulators such as phospholipid PIP2, 2-aminoethoxydiphenyl borate (2-APB), and cannabinoid, while other ligands are more specific, such as allyl isothiocyanate (TRPA1), vanilloids (TRPV1), menthol (TRPM8), ADP-ribose (TRPM2), and ML-SA1 (TRPML1). The mechanisms underlying the gating and regulation of TRP channels remain largely unclear. Recent advances in cryogenic electron microscopy provided structural insights into 19 different TRP channels which all revealed close proximity of the C-terminus with the N-terminus and intracellular S4-S5 linker. Further studies found that some highly conserved residues in these regions of TRPV, -P, -C and -M members mediate functionally critical intramolecular interactions (i.e., within one subunit) between these regions. This review provides an overview on (1) intramolecular interactions in TRP channels and their effect on channel function; (2) functional roles of interplays between PIP2 (and other ligands) and TRP intramolecular interactions; and (3) relevance of the ligand-induced modulation of intramolecular interaction to diseases.© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.