The diverse forms and roles of the neuronal endoplasmic reticulum.

Abstract

Neurons are structurally complex and highly compartmentalized, placing unique demands on organelles to adapt locally and support communication across long distances. The endoplasmic reticulum (ER) meets this challenge through a dynamic and versatile architecture that spans the entire neuron. While specialized ER structures in axons, dendrites and synapses have been recognized for some time, recent work has uncovered new insights into their local functions and interactions with other membranes. In this Review, we highlight how neuronal ER morphology is established in different subcellular domains, including somato-dendritic regions, axons, and presynaptic and postsynaptic sites. These distinct ER structures enable localized functions in Ca²⁺ signalling, biosynthesis, excitability, regeneration, synaptic transmission and plasticity. We also discuss how perturbations in the ER contribute to neurodegenerative diseases.