Until now, many selective cathepsin inhibitors such as CA-074 and E-64c,d with limited adverse effects were developed and showed neuroprotection in the cerebral ischemia models of monkeys (Yamashima et al., 1998) and are awaiting validation in the clinical setting for Alzheimer’s disease (Hook et al., 2020). Here, CTSS is linked to early-onset autosomal dominant Alzheimer disease.