Decreased CTSD protein levels or the loss of protease activity can impair autophagy-lysosomal function and induce the intracellular accumulation of proteins associated with disease development, which are involved in the pathological processes of many different types of diseases, including neurodegenerative diseases (Bunk et al., 2021), stroke (Hossain et al., 2021), and fatty liver (Jeong et al., 2021). Here, CTSD is linked to neurodegenerative disease.