SGCB encodes β-sarcoglycan, a transmembrane protein component of the sarcoglycan complex within the dystrophin-glycoprotein complex (DGC) located at the sarcolemma 1. Together with α-, γ-, and δ-sarcoglycan, β-sarcoglycan forms a four-protein transmembrane complex that functions as a mechanical linker between the F-actin cytoskeleton and extracellular matrix, providing critical support during myofiber contraction 12. Biallelic loss-of-function SGCB mutations cause limb-girdle muscular dystrophy type R4/LGMD2E, classified among the most severe forms of autosomal recessive LGMDs, constituting 10-25% of all LGMD cases 13. Patients typically present with disease onset in the first decade of life, exhibiting muscle hypertrophy, elevated creatine kinase, progressive muscle weakness, and variable loss of ambulation 13. Animal models show early and progressive fibrosis with greater connective tissue deposition than dystrophin-deficient models 4. Recent advances include AAV-based gene therapy (bidridistrogene xeboparvovec) that functionally replaces deficient SGCB protein; Phase 1/2 trials demonstrated robust SGCB expression (36-62% of normal) and preliminary motor improvements in pediatric patients 5. Functional characterization of variants predicts pathogenicity and correlates with disease severity 2.