BACKGROUND: Calpainopathies, including limb-girdle muscular dystrophy recessive type 1 (LGMD R1) and the rare dominant type 4 (LGMD D4), are genetic neuromuscular disorders caused by pathogenic variants in the CAPN3 gene, which encodes calpain-3, a muscle-specific cysteine protease. The gene discussed is CTSB; the disease is autosomal recessive limb-girdle muscular dystrophy type 2A.