Several genetic diseases are caused by missense mutations leading to the proteasomal degradation of misfolded proteins through the endoplasmic reticulum quality control process (ERQC). Among these diseases, limb-girdle muscular dystrophies type 2D (LGMD2D) is characterized by a progressive proximal muscle weakness. Molecularly, LGMD2D is due to mutations in the gene encoding alpha–sarcoglycan (alpha-SG), a dystrophin-associated glycoprotein. Recent findings described the positive impact of ERQC inhibitors on alpha-SG localization to the plasma membrane leading to the development of new therapeutical perspectives. Here, we report the development of a new in vitro high-throughput screening assay that allow to monitor the proper localization of the most frequent mutant form of alpha-SG (R77C substitution). Using this pharmacological assay, a library of 2200 FDA-approved drugs was tested identifying a list of new drug candidates potentially repurposable to LGMD2D.