Without retromer, CI-MPR (red) leaks through to late endosomes and lysosomes (green).

Helping to create the lysosome is a dangerous job—stick with your task for too long and you might end up as dinner. Seaman (page 111) and Arighi et al. (page 123) now describe how the cation-independent mannose 6-phosphate receptor (CI-MPR) escorts lysosomal enzymes toward their future home but then escapes just in time thanks to a complex of proteins called the retromer.

The retromer was first characterized in yeast, where it drags Vps10p from endosomes back to the Golgi. Vps10p and the mammalian CI-MPR have no sequence homology but do perform similar functions. So the researchers tested whether the retromer could also rescue CI-MPR.

They first confirmed that both CI-MPR and the mammalian retromer are located in endosomes, with additional CI-MPR in the trans-Golgi network. After either knockout or...

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