PRKN and Parkinson disease: Currently, most researchers postulate that defects in the retromer machinery affect the proteostasis and cellular burden of cytotoxic proteins including α-syn and Aβ; however, the causal relationship between these protein aggregates and neuronal cell loss is unclear, especially in PD because patients with PARK2 typically display pure nigral degeneration without LBs, and LB pathology may not be present in patients with dominantly inherited familial PD with LRRK2 and VPS35 mutations (Hayashi et al., 2000; Hasegawa et al., 2009; Bono et al., 2020).