The cation-independent mannose 6-phosphate receptor (CIMPR) cycles between the 
trans-Golgi network (TGN) and endosomes to mediate sorting of lysosomal 
hydrolases. The endosome-to-TGN retrieval of the CIMPR requires the retromer 
complex. Genetic, biochemical and structural data support the hypothesis that 
the retromer can directly bind to the tail of the CIMPR, to sort the CIMPR into 
vesicles and tubules for retrieval to the TGN. Presently, however, no known 
retromer sorting motif in the tail of the CIMPR has been identified. Using 
CD8-reporter proteins carrying the cytoplasmic tail of the CIMPR we have 
systematically dissected the CIMPR tail to identify a novel, conserved 
aromatic-containing sorting motif that is critical for the endosome-to-TGN 
retrieval of the CIMPR and for the interaction with retromer and the clathrin 
adaptor AP-1.