Interestingly, like EOFAD mutant forms of PSEN1 (Lee et al., 2010) and the C99 fragment of APP (Jiang et al., 2019), the ε4 allele of APOE has been shown to affect both lysosomal pH (Prasad and Rao, 2018) and the MAM (Tambini et al., 2016). Here, APOE is linked to early-onset autosomal dominant Alzheimer disease.