CASQ1 encodes calsequestrin-1, a high-capacity calcium-binding protein that serves as the primary calcium buffer in the sarcoplasmic reticulum (SR) of skeletal muscle fibers 1. The protein can bind approximately 80 calcium ions and regulates calcium release through ryanodine receptor type-1 (RyR1), playing a crucial role in excitation-contraction coupling and muscle contraction 12. CASQ1 functions through calcium-dependent polymerization and physically interacts with RyR1 to modulate its activity 3. Additionally, CASQ1 negatively regulates store-operated calcium entry (SOCE), preventing excessive calcium influx when SR stores are depleted 42. Mutations in CASQ1 cause tubular aggregate myopathy (TAM), characterized by muscle weakness and accumulation of SR tubules 14. Disease-associated mutations impair calcium-dependent aggregation, reduce calcium storage capacity, and diminish SOCE inhibition 14. CASQ1 deficiency is also associated with malignant hyperthermia susceptibility and heat stroke, as CASQ1-knockout mice exhibit excessive SR calcium leak and are prone to sudden death under heat or anesthetic exposure 52. The protein is also expressed in cardiac muscle, where its deficiency contributes to arrhythmias 3.