UC Davis

Membrane contact sites (MCSs) are specialized regions where two or more organelle membranes come into close apposition, typically separated by only 10-30 nm, while remaining distinct and unfused. These sites play crucial roles in cellular homeostasis, signaling, and metabolism. This review focuses on ion channels, transporters, and receptors localized to MCSs, with particular emphasis on those associated with the plasma membrane and endoplasmic reticulum (ER). We discuss the molecular composition and functional significance of these proteins in shaping both organelle and cellular functions, highlighting their importance in excitable cells and their influence on intracellular calcium signaling. Key MCSs examined include ER-plasma membrane, ER-mitochondria, and ER-lysosome contacts. This review addresses our current knowledge of the ion channels found within these contacts, the dynamic regulation of MCSs, their importance in various physiological processes, and their potential implications in pathological conditions.