Endosomes as central hubs of interorganellar communication and cellular homeostasis.

Endocytosis mediates the internalization of extracellular cargo via vesicular trafficking, enabling targeted delivery to specific organelles and maintaining cellular homeostasis. Endosomes function as dynamic hubs that orchestrate intracellular communication. While they primarily internalize material from the cell surface, their role extends far beyond passive transport. Through continuous cycles of sorting, fusion, and fission, endosomes engage in extensive crosstalk with other organelles via three fundamental modes: vesicle-mediated cargo transport, membrane contact site-mediated non-vesicular exchange, and signaling and mechanical coupling. These interorganellar interactions enable the transfer of metabolites, lipids, and signals, positioning endosomes as central regulators of cellular homeostasis. While interest in these contacts is growing, a systematic understanding of their roles is still needed. This review explores the protein machinery involved, examines how endosome-organelle contacts coordinate transport and remodeling, and discusses their impact on homeostasis and disease when dysregulated. We underscore the importance of the endosomal communication network in adaptive responses and provide perspectives for targeting endosome-related pathologies.