Calsequestrin (CASQ) (CASQ)

Calsequestrin is a high-capacity, moderate-affinity calcium-binding protein located within the lumen of the sarcoplasmic reticulum (SR) in cardiac and skeletal muscle cells (UniProt, 2024). It serves as the primary calcium buffer, allowing for the storage of large amounts of calcium ions while maintaining a relatively low free calcium concentration, which is essential for muscle contraction and relaxation cycles (PubMed, 2021). Calsequestrin exists in two main isoforms: CASQ1, found primarily in skeletal muscle, and CASQ2, which is the predominant form in cardiac muscle (NCBI, 2023). Beyond its role as a buffer, it acts as a luminal calcium sensor that modulates the activity of the ryanodine receptor (RyR) calcium release channel through interactions with proteins like triadin and junctin (StatPearls, 2023). Mutations in the CASQ2 gene are a known cause of catecholaminergic polymorphic ventricular tachycardia (CPVT), a life-threatening arrhythmia triggered by exercise or stress (NIH, 2022). While few drugs target calsequestrin directly, it is a critical component of the calcium-release complex targeted by anti-arrhythmic agents like flecainide and muscle relaxants like dantrolene (Journal of Biological Chemistry, 2020). Therapeutic strategies focusing on stabilizing the interaction between calsequestrin and the RyR complex are currently being explored to treat calcium-handling disorders (PubMed, 2021).

Other names

CSQCalsequestrin-1Calsequestrin-2CASQ1CASQ2

Calsequestrin acts as a high-capacity calcium buffer and a regulator of the ryanodine receptor (RyR) complex, modulating calcium release from the sarcoplasmic reticulum (PubMed, 2021).