SGCA encodes alpha-sarcoglycan, a critical component of the sarcoglycan complex within the dystrophin-glycoprotein complex (DGC) that provides mechanical support to muscle sarcolemma during fiber contraction 1. The DGC acts as a linker between the muscle fiber cytoskeleton and extracellular matrix, maintaining sarcolemma integrity during muscle contraction 1. Mutations in SGCA cause LGMDR3 (limb-girdle muscular dystrophy type R3), one of the most severe forms of autosomal recessive limb-girdle muscular dystrophies 1. LGMDR3 typically presents in the first decade of life with muscle hypertrophy, elevated creatine kinase, variable muscle weakness, and progressive loss of ambulation 1. In a large European cohort, SGCA mutations accounted for 159 of 396 sarcoglycanopathy cases, with patients showing later onset and slower disease progression compared to other sarcoglycanopathy subtypes 2. Common pathogenic variants include c.229C>T, c.739G>A, and c.850C>T, found in 60% of LGMDR3 patients 2. Clinical significance includes the identification of early symptom onset (before age 10) and low residual protein expression (<30%) as risk factors for early loss of ambulation 2. Gene therapy approaches using adeno-associated virus vectors for sarcoglycan replacement are under development 1.