CTSB and Down syndrome: Notably, v-ATPase impairments have been linked to lysosomal acidification dysfunction in Down syndrome and AD66,67 as well as in APOE4 mice68, supporting the proposed framework of early lysosomal dysfunction in AD.69Lamp1 and Cathepsin B (Ctsb) are core components of the lysosomal degradation machinery and were recently identified as critical hub genes of lysosomal dysfunction in AD70.