The Ragulator complex: delving its multifunctional impact on metabolism and beyond

Our understanding of lysosomes has undergone a significant transformation in recent years, from the view that they are static organelles primarily responsible for the disposal and recycling of cellular waste to their recognition as highly dynamic structures. Current research posits that lysosomes function as a signaling hub that integrates both extracellular and intracellular stimuli, thereby regulating cellular homeostasis. The dysregulation of lysosomal function has been linked to a wide range of diseases. Of note, lysosomes contribute to the activation of mammalian target of rapamycin complex 1 (mTORC1), a key regulator of cellular metabolism. The Ragulator complex, a protein complex anchored on the lysosomal membrane, was initially shown to tether the mTORC1 complex to lysosomes. Recent research has substantially expanded our understanding of the roles of the Ragulator complex in lysosomes, including roles in the regulation of metabolism, inflammation, cell death, cell migration, and the maintenance of homeostasis, via interactions with various proteins. This review summarizes our current knowledge on the diverse functions of the Ragulator complex, highlighting important protein interactions.