The functioning of the retromer complex has been linked to two distinct neurological diseases, Parkinson's disease (PD) and Alzheimer's disease (AD) (Small and Petsko, 2015; McMillan et al., 2017). A mutation in VPS35 (D620N) that causes an inherited form of PD results in reduced association of the WASH complex with the retromer CSC and therefore less WASH complex is recruited to the endosome (Zavodszky et al., 2014). This is because the D620N mutation reduces the binding affinity of VPS35 for the WASH complex protein Fam21 (McGough et al., 2014). The AD-linked mutation in VPS35 destabilises the retromer CSC by impairing the binding of VPS35 to VPS29 (Rovelet-LeCrux et al., 2015). It has been reported that levels of the retromer CSC are reduced in the brains of AD patients and knockdown of VPS35 results in increased processing of amyloid precursor protein (APP) to the pro-aggregatory neurotoxic Aβ peptide (Small et al., 2005; Muhammad et al., 2008). Variants of the Snx3 and Rab7a genes required for the recruitment of the retromer CSC are linked to late-onset AD and hence retromer function has
