SGCD encodes delta-sarcoglycan, a critical component of the sarcoglycan complex within the dystrophin-glycoprotein complex (DGC) 1. This protein functions as a structural linker between the F-actin cytoskeleton and the extracellular matrix at the muscle sarcolemma, providing mechanical support during myofiber contraction 1. Mutations in SGCD cause LGMDR6 (limb-girdle muscular dystrophy autosomal recessive 6), one of four sarcoglycanopathies that constitute 10-25% of all autosomal recessive LGMDs 1. SGCD-related disease typically manifests in the first decade of life with muscle hypertrophy, elevated creatine kinase, progressive weakness, and variable ambulation loss 1. Cardiac and respiratory involvement occur across sarcoglycanopathy subtypes 2. Pathologically, SGCD deficiency destabilizes the DGC, rendering muscle fibers vulnerable to contraction-induced damage 3. Early dysregulation of ATX-LPA and YAP/TAZ signaling pathways promotes inflammation and fibrosis in SGCD-deficient skeletal muscle 3. Risk factors for early ambulation loss include symptom onset before age 10 and residual protein expression below 30% 4. Gene replacement therapy using adeno-associated virus vectors shows promise in preclinical models and ongoing human trials 1, 5.