IST1 and proteostasis deficiencies: In addition to mitochondrial targets, endolysosomal dysfunction has been linked to the disruption of vacuolar ATPase (V-ATPase) activity, a decrease in neuronal FKBP4/FKBP52, and inhibition of IST1 (IST1 factor associated with ESCRT-III) expression, which mediates the proteopathy and impairs autophagosome–lysosome fusion53–55.