Trafficking to the lysosome: HOPS paves the way

The endo-lysosomal system plays a crucial role in cellular homeostasis by continuously turning over organelles, proteins, and other cargo of intra- or extracellular origin. Moreover, it senses the nutrient status within the cell and can ignite cellular responses by activating or repressing signaling pathways. To enable these roles, lysosomes are fueled by the biosynthetic pathway and receive cargo for degradation by endocytosis and autophagy. Tight regulation and coordination of these distinct trafficking pathways to lysosomes are critical for cellular health. In this review, we explore how these pathways converge at the late stages of the endo-lysosomal system and highlight the role of the HOPS complex as a unifying gatekeeper for trafficking to the lysosome.