For example, α-synuclein was found to behave as a TFEB-sequestering molecule to accumulate TFEB in the Lewy bodies, thereby hindering TFEB from nuclear translocation in dopaminergic neurons of Parkinson’s disease (Decressac et al., 2013); and apolipoprotein E4 (apoE4), which is encoded by the APOE ε4 allele, the single greatest risk factor for Alzheimer’s disease in humans, was shown to compete with TFEB in binding to the CLEAR motif in the promoter of lysosomal genes (Parcon et al., 2018). Here, APOE is linked to early-onset autosomal dominant Alzheimer disease.