Inclusion Criteria: * Cohort 1, only ambulatory participants: * Able to walk without assistive aid * 10MWR \<30 seconds * NSAD ≥25 * Cohort 2, only non-ambulatory participants: * 10MWR ≥30 seconds or unable to perform * PUL 2.0 entry scale score ≥3 * Participants must possess 1 homozygous or 2 heterozygous pathogenic and/or likely pathogenic β-SG DNA gene mutations * Able to cooperate with muscle testing * Participants must have adeno-associated virus serotype rh74 (AAVrh74) antibody titers \<1:400 (that is, not elevated) as determined by AAVrh74 antibody enzyme-linked immunosorbent assay. Exclusion Criteria: * Left ventricular ejection fraction \< 40% or clinical signs and/or symptoms of cardiomyopathy * Forced vital capacity ≤40% of predicted value and/or requirement for nocturnal ventilation * Diagnosis of (or ongoing treatment for) an autoimmune disease and on active immunosuppressant treatment * Presence of any other clinically significant illness or medical condition (other than LGMD2E/R4) Other inclusion/exclusion criteria apply.