The retromer complex is a key player in endosomal protein sorting and is conserved across all eukaryotes. Retromer comprises two functional units that, in higher eukaryotes such as mammals, associate loosely to mediate the sorting and transport of proteins from endosomes to either the Golgi or the cell surface (Seaman, 2012; Burd and Cullen, 2014). A stable trimeric complex of VPS35, VPS29 and VPS26 is important in selecting membrane proteins (cargo) and is often referred to as the cargo-selective complex (CSC). Formation of tubular carriers is mediated by a dimer of Bin/amphiphysin/Rvs domain-containing sorting nexin (SNX-BAR) proteins containing either Snx1 or Snx2 bound to Snx5 or Snx6 (van Weering et al., 2012). The SNX-BAR proteins have also been reported to interact with some cargo proteins, notably the cation-independent mannose 6-phosphate receptor (CIMPR) (Kvainickas et al., 2017; Simonetti et al., 2017).
