Lysosomal dysfunction plays a key role in the pathogenesis of Alzheimer’s disease and Parkinson’s disease. In early onset of Alzheimer’s disease, there is loss of Presenilin-1 (PSEN1) function. The loss of PSEN1 function interferes with ER to lysosome delivery of chloride channel-7. For this study, isoproterenol and related β2-adrenergic agonists was used to reverse lysosomal chloride deficits in murine blastocysts with different PSEN1 genotypes. This dataset contains RNA sequencing data of PSEN1 KO and WT murine blastocysts cells with and without isoproterenol treatment. The results 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.