ER morphology and endo-lysosomal crosstalk: Functions and disease implications

The endoplasmic reticulum (ER) is a continuous endomembrane system comprising the nuclear envelope, ribosome-studded sheets, dense peripheral matrices, and an extensive polygonal network of interconnected tubules. In addition to performing numerous critical cellular functions, the ER makes extensive contacts with other organelles, including endosomes and lysosomes. The molecular and functional characterization of these contacts has advanced significantly over the past several years. These contacts participate in key functions such as cholesterol transfer, endosome tubule fission, and Ca²⁺ exchange. Disruption of key proteins at these sites can result in often severe diseases, particularly those affecting the nervous system.