Proposed model for LE/MVB trafficking prior to exosome release under steady state conditions. Dynamic ORP1L-mediated ER-LE/MVB membrane contact sites ensure maturation and RILP/dynein-mediated transport of non-catalytic CD63/LAMP1/Rab7⁺ ECV/MVB toward the MTOC. This centripetal movement subsequently facilitates the switch from Rab7 to Arl8b, which in turn allows kinesin-mediated transport toward the periphery and a switch from Arl8b to Rab27a, bypassing lysosomal compartments, and rendering CD63/LAMP1⁺ LE competent to fuse with the plasma membrane (PM). EE, early endosome; ECV, Endocytic Carrier Vesicles; MVB, multivesicular bodies; LE, late endosome; L, lysosome; E/L, endolysosome; MTOC, microtubule-organizing center. Microtubules are depicted in green.