Calsequestrin is the major Ca²⁺ binding protein in the sarcoplasmic reticulum (SR), serves as the main Ca²⁺ storage and buffering protein and is an important regulator of Ca²⁺ release channels in both skeletal and cardiac muscle. It is anchored at the junctional SR membrane through interactions with membrane proteins and undergoes reversible polymerization with increasing Ca²⁺ concentration. Calsequestrin provides high local Ca²⁺ at the junctional SR and communicates changes in luminal Ca²⁺ concentration to Ca²⁺ release channels, thus it is an essential component of excitation-contraction coupling. Recent studies reveal new insights on calsequestrin trafficking, Ca²⁺ binding, protein evolution, protein-protein interactions, stress responses and the molecular basis of related human muscle disease, including catecholaminergic polymorphic ventricular tachycardia (CPVT). Here we provide a comprehensive overview of calsequestrin, with recent advances in structure, diverse functions, phylogenetic analysis, and its role in muscle physiology, stress responses and human pathology.

Calsequestrin 是肌浆网 (SR) 中的主要 Ca ²⁺结合蛋白，作为主要的 Ca ²⁺储存和缓冲蛋白，是骨骼肌和心肌中 Ca ²⁺释放通道的重要调节剂。它通过与膜蛋白的相互作用锚定在连接的 SR 膜上，并随着 Ca ²⁺浓度的增加进行可逆聚合。Calsequestrin在交界处提供高局部 Ca ²⁺并将管腔 Ca ²⁺浓度的变化传达给 Ca ²⁺释放通道，因此它是兴奋收缩耦合的重要组成部分。最近的研究揭示了关于钙螯合蛋白运输、Ca ²⁺结合、蛋白质进化、蛋白质-蛋白质相互作用、应激反应和相关人类肌肉疾病（包括儿茶酚胺多形性室性心动过速 (CPVT)）的分子基础的新见解。在这里，我们提供了 calsequestrin 的全面概述，包括结构、不同功能、系统发育分析的最新进展及其在肌肉生理学、应激反应和人类病理学中的作用。