The cell’s major fibronectin-binding integrin (α5β1) promotes survival and migration of tumor cells (Caswell et al., 2008 and Lee and Juliano, 2000), making this an important molecule for cell biologists interested in cancer progression. α5β1 integrin is continuously internalized, trafficked to recycling endosomes and then returned, or recycled, to the plasma membrane via both Rab11- and Arf6-dependent pathways (Caswell and Norman, 2006 and Pellinen and Ivaska, 2006). However, α5β1 integrins that are ligand-engaged do not reach recycling endosomes but are sent to lysosomes under control of Rab25 (Dozynkiewicz et al., 2012, Lobert et al., 2010 and Rainero and Norman, 2013). Moreover, Rab25 expression is associated with upregulation of a lysosomal protein called CLIC3, which prevents degradation of α5β1 and allows recycling from this compartment to the plasma membrane (Dozynkiewicz et al., 2012).