Figure 1. Intracellular trafficking mediated by retromer complex and PD-associated retromer variants.

Retrograde cargo trafficking from endosomes to the TGN is mediated through numerous pathways including retromer-dependent and independent pathways. The Retromer complex is also required for cargo recycling from the endosome back to plasma membrane. In contrast, PD-associated retromer Vps35 D620N variant is associated with changes in cargo trafficking itinerary due to the impaired binding of retromer with the WASH complex, which results in defects in formation of retrograde ETC and possibly recycling of cargo to the plasma membrane.