Lysosomal dysfunction plays a key role in the pathogenesis of Alzheimer’s disease (AD) and Parkinson’s disease (PD). In early onset of AD, there is loss of Presenilin-1 (PSEN1) function. The loss of PSEN1 function impedes ER to lysosome delivery of chloride channel-7 (ClC-7). In murine blastocysts with different PSEN1 genotypes, isoproterenol and related β2-adrenergic agonists was used to reverse lysosomal chloride deficits. The dataset contains RNA sequencing data from mice with and without isoproterenol (ISO) treatment. Transcriptomics of PSEN1 deficient cells revealed strongly down regulated ER to lysosome transport pathways. This study showed that isoproterenol and related β2-adrenergic agonists re-acidify lysosomes in PSEN1 KO cells, which restores lysosomal proteolysis, calcium homeostasis, and normal autophagy flux.