AP-4 regulates neuronal lysosome composition, function, and transport via regulating export of critical lysosome receptor proteins at the trans-Golgi network

Using CRISPRi-based depletion in human iPSC-derived neurons we demonstrate that AP-4 adaptor protein complex regulates neuronal lysosome composition and function via regulating sorting of critical lysosomal protein receptors including Sortilin 1 to the organelle. AP-4 also regulates axonal endo-lysosome abundance in these human neurons.