LRRK2 and Parkinson disease: PD-associated LRRK2 mutant G2019S has decreased binding activity to these E3 ligases, resulting in increased phosphorylation and activation of E3 ubiquitin ligases by PERK, which consequently causes increased degradation of MERCS tethering proteins and reduced ER-mitochondrial contacts (Figure 4; Toyofuku et al., 2020).