Sarcolipin (SLN) is a small regulatory protein that reversibly inhibits the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) pump by decreasing the apparent affinity of SERCA1 and SERCA2 for Ca2+ 1. SLN uncouples SERCA Ca2+ transport from ATP consumption, directly modulating skeletal muscle relaxation and energy expenditure 1. The protein comprises 31 amino acids with a single transmembrane helix, and is highly expressed in fast-twitch skeletal muscle but expressed at lower levels in slow-twitch muscle and cardiac tissue 2. SLN plays a critical role in non-shivering thermogenesis and calcium homeostasis during muscle adaptation. During muscle development, overload, and atrophy, SLN expression increases dynamically and activates Ca2+ signaling to promote mitochondrial biogenesis, fiber-type shifts, and muscle hypertrophy 1. In muscle disease contexts, SLN upregulation demonstrates a hormesis effect—both excessive and insufficient SLN levels are detrimental to muscle health 1. While some evidence suggests elevated SLN in dystrophic muscle may exacerbate calcium dysregulation, growing literature indicates SLN upregulation protects the SERCA pump and facilitates adaptive remodeling during cellular stress 1. Mutations in the SLN gene have been investigated in Brody disease, an inherited skeletal muscle disorder affecting relaxation, though structural SLN mutations were not identified in examined patients 2.