Calsequestrin (CASQ) is the most abundant Ca²⁺ binding protein localized in the sarcoplasmic reticulum (SR) of skeletal and cardiac muscle. The genome of vertebrates contains two genes, CASQ1 and CASQ2. CASQ1 and CASQ2 have a high level of homology, but show specific patterns of expression. Fast-twitch skeletal muscle fibers express only CASQ1, both CASQ1 and CASQ2 are present in slow-twitch skeletal muscle fibers, while CASQ2 is the only protein present in cardiomyocytes. Depending on the intraluminal SR Ca²⁺ levels, CASQ monomers assemble to form large polymers, which increase their Ca²⁺ binding ability. CASQ interacts with triadin and junctin, two additional SR proteins which contribute to localize CASQ to the junctional region of the SR (j-SR) and also modulate CASQ ability to polymerize into large macromolecular complexes. In addition to its ability to bind Ca²⁺ in the SR, CASQ appears also to be able to contribute to regulation of Ca²⁺ homeostasis in muscle cells. Both CASQ1 and CASQ2 are able to either activate and inhibit the ryanodine receptors (RyRs) calcium release channels, likely through their interactions with junctin and triadin. Additional evidence indicates that CASQ1 contributes to regulate the mechanism of store operated calcium entry in skeletal muscle via a direct interaction with the Stromal Interaction Molecule 1 (STIM1). Mutations in CASQ2 and CASQ1 have been identified, respectively, in patients with catecholamine-induced polymorphic ventricular tachycardia and in patients with some forms of myopathy. This review will highlight recent developments in understanding CASQ1 and CASQ2 in health and diseases.

Calsequestrin (CASQ) 是位于骨骼肌和心肌的肌质网 (SR) 中最丰富的 Ca ^{2+结合蛋白。}脊椎动物的基因组包含两个基因，CASQ1和CASQ2。CASQ1 和 CASQ2 具有高度同源性，但表现出特定的表达模式。快肌骨骼肌纤维仅表达 CASQ1，慢肌骨骼肌纤维中同时存在 CASQ1 和 CASQ2，而心肌细胞中仅存在 CASQ2 蛋白。根据管腔内 SR Ca ²⁺水平，CASQ 单体组装形成大聚合物，从而增加其 Ca ²⁺绑定能力。CASQ 与 triadin 和 junctin 相互作用，这两种额外的 SR 蛋白有助于将 CASQ 定位到 SR (j-SR) 的连接区域，并调节 CASQ 聚合成大分子复合物的能力。除了在 SR 中结合 Ca ²⁺的能力外，CASQ 似乎还能够促进 Ca ^2+的调节肌肉细胞的稳态。CASQ1 和 CASQ2 都能够激活和抑制兰尼碱受体 (RyRs) 钙释放通道，可能是通过它们与 junctin 和 triadin 的相互作用。其他证据表明，CASQ1 通过与基质相互作用分子 1 (STIM1) 的直接相互作用，有助于调节储存操作的钙进入骨骼肌的机制。CASQ2 和 CASQ1 的突变分别在儿茶酚胺诱导的多形性室性心动过速患者和某些形式的肌病患者中被发现。本综述将重点介绍了解 CASQ1 和 CASQ2 在健康和疾病方面的最新进展。