The present discloure provides biglycan-related therapeutic polypeptides comprising substitutions at two serine residues such that the polypeptide does not comprise any glycosaminoglycan side chains. Further provided are methods for treating diseases or conditions associated with an abnormal level or activity of biglycan disorders associated with an unstable cytoplasmic membrane, for example, due to an unstable dystrophin associated protein complex (DAPC) disorders associated with abnormal synapses or neuromuscular junctions, including those resulting from an abnormal MuSK activation or acetylcholine receptor (AChR) aggregation. Examples of diseases include muscular dystrophies, such as Duchennes Muscular Dystrophy, Beckers Muscular Dystrophy, neuromuscular disorders and neurological disorders.
