Discovery and Roles of ER-Endolysosomal Contact Sites in Disease

Inter-organelle membrane contact sites (MCSs) serve as unique microenvironments for the sensing and exchange of cellular metabolites and lipids. Though poorly defined, ER-endolysosomal contact sites are quickly becoming recognized as centers for inter-organelle lipid exchange and metabolic decision-making. Here, we review the discovery and current state of knowledge of ER-endolysosomal MCSs with particular focus on the molecular players that establish and/or utilize these contact sites in metabolism. We also discuss associations of ER-endolysosomal MCS-associated proteins in human disease, as well as the therapeutic promise these contact sites hold in modulating cellular physiology.