Although TRIM21 is only expressed at low levels in the brain (Zhang et al., 2014; Uhlén et al., 2015), it is sufficient to clear both α-synuclein and tau aggregates through an antibody-mediated mechanism reminiscent of its well-documented function in clearing viral substrates, implicating it in repressing AD and PD (Mallery et al., 2010; Kondo et al., 2015; McEwan et al., 2017). Here, MAPT is linked to Alzheimer disease.