Sarcospan (SSPN) is a component of the dystrophin-glycoprotein complex (DGC), which links the F-actin cytoskeleton to the extracellular matrix in muscle 1. SSPN preferentially associates with the sarcoglycan subcomplex and is expressed in vascular smooth muscle and endothelial cells, where it colocalizes with dystrophin, utrophin, and caveolin 1. Beyond skeletal muscle, SSPN plays critical roles in cardiac function and metabolic homeostasis. Genome-wide association studies identified SSPN as a risk locus for atrial fibrillation, likely through cardiac structural remodeling mechanisms 2, and as a putative effector gene in dilated cardiomyopathy pathogenesis 3. In vivo studies demonstrate that SSPN deficiency protects mice from diet-induced obesity but reveals sex-dependent metabolic consequences: aged SSPN-deficient males develop diastolic dysfunction and increased left ventricular mass, while females develop glucose intolerance 4. These findings suggest SSPN functions in both striated muscle structural integrity and systemic metabolic regulation, with important implications for understanding sex-dependent susceptibility to cardiometabolic diseases.