ATP2A1 encodes SERCA1 (sarco/endoplasmic reticulum Ca2+ ATPase isoform 1), a critical regulator of skeletal muscle calcium homeostasis. SERCA1 actively transports calcium from the cytosol into the sarcoplasmic reticulum using ATP hydrolysis, a process essential for muscle relaxation following contraction 1. The pump is predominantly expressed in type II skeletal muscle fibers and plays a central role in maintaining appropriate calcium levels required for excitation-contraction coupling. Loss-of-function mutations in ATP2A1 cause autosomal recessive Brody myopathy, characterized by impaired muscle relaxation and exercise-induced muscle stiffness 1. In knockout mouse models, SERCA1 deficiency reduces calcium transport activity by ~80% and causes severe contractile dysfunction, particularly in the diaphragm, leading to neonatal respiratory failure 2. The critical importance of SERCA1 is further demonstrated by a bovine animal model carrying an ATP2A1 missense mutation (p.Arg164His) that phenocopies human Brody disease 3. Beyond skeletal muscle, emerging evidence suggests ATP2A1 has broader relevance. Mendelian randomization studies identified ATP2A1 as a potential therapeutic target for cognitive performance 4 and rheumatoid arthritis 5, though mechanisms remain unclear. Additionally, ATP2A1 expression alterations have been associated with breast cancer progression 6. These findings suggest ATP2A1 function extends beyond classical calcium regulation in muscle physiology.