RYR1 encodes the ryanodine receptor 1 (RyR1), a calcium-activated calcium channel located on the skeletal muscle sarcoplasmic reticulum that mediates calcium release into the cytoplasm, playing a critical role in excitation-contraction coupling and muscle contraction 1. The protein comprises 5,038 amino acids and is fundamental to skeletal muscle calcium homeostasis 1. Pathogenic RYR1 mutations destabilize the channel, leading to pathologic calcium leak from the sarcoplasmic reticulum, which causes oxidative stress and muscle dysfunction 2. This calcium leak increases activity of calcium-activated proteases and contributes to muscle damage 2. RYR1 mutations are associated with multiple disorders including malignant hyperthermia susceptibility, central core disease, multi-minicore disease, and other RYR1-related myopathies 134. These conditions exhibit highly heterogeneous clinical phenotypes ranging from asymptomatic hyperCKemia to severe muscle weakness and respiratory impairment 43. Recent therapeutic approaches target calcium leak stabilization, with RyR1-stabilizing compounds like Rycals showing promise in clinical trials for treating RYR1-related myopathies 52. The genetic basis shows both autosomal dominant and recessive inheritance patterns depending on the specific mutation and associated phenotype 6.