SGCG encodes gamma-sarcoglycan, a core component of the sarcoglycan complex within the dystrophin-glycoprotein complex (DGC) 1. This complex functions as a mechanical linker between the F-actin cytoskeleton and the extracellular matrix at the sarcolemma, providing critical support during myofiber contraction 1. The sarcoglycan complex coordinates phosphorylation and calcium flux during mechanical deformation, with novel interacting partners including NKCC1 and protein phosphatase 1 identified as potential regulators of mechano-signaling 2. Loss-of-function SGCG mutations cause LGMDR5 (limb-girdle muscular dystrophy autosomal recessive type 5), the most severe form of autosomal recessive LGMD 1. Patients typically present with onset before age ten, muscle hypertrophy, elevated creatine kinase, progressive weakness, and loss of ambulation 13. Cardiac and respiratory involvement occurs in approximately 17% and 14% of sarcoglycanopathy patients respectively, with cardiac abnormalities being most frequent in LGMDR4 4. SGCG variants also associate with atrial fibrillation susceptibility as identified in genome-wide association studies, suggesting roles in cardiac structural remodeling 5. Gene replacement therapy using adeno-associated viral vectors shows promise in preclinical models with detectable protein restoration and phenotypic improvement 1.