Model. In control cells, two mutually exclusive, synchronous events take place on late endosomes/lysosomes. On the one hand, the BORC–LAMTOR interaction blocks recruitment of Arl8b and leads to the perinuclear position of late endosomes. On the other hand, the BORC­–Arl8b interaction promotes the transport of late endosomes, resulting in a peripheral distribution. The steady-state scenario is a combination of both, with some late endosomes being transported toward the cell periphery, whereas others remain perinuclear. In lyspersin KO cells, the remaining subunits of BORC (BORCΔlyspersin) are insufficient to recruit Arl8b to late endosomes, resulting in perinuclear clustering of the organelles. Lyspersin depletion also prevents LAMTOR–BORCΔlyspersin interaction. Depletion of the LAMTOR complex increases BORC–Arl8b interaction, thereby promoting transport and peripheral accumulation of LAMP1-positive endosomes. Yellow trapezoid, LAMTOR complex; dark blue trapezoid, BORCΔlyspersin; light blue shape, lyspersin with discrimination of individual domains (N-domain, PRR, and C-domain); red shape, Arl8b.