The heterogeneity of the endoplasmic reticulum (ER) makes it a versatile platform for a broad range of homeostatic processes, ranging from calcium regulation to synthesis and trafficking of proteins and lipids. It is not surprising that neurons use this organelle to fine-tune synaptic properties and thereby provide specificity to synaptic inputs. In this review, we discuss the mechanisms that enable activity-dependent ER recruitment into dendritic spines, with a focus on molecular mechanisms that mediate transport and retention of the ER in spines.
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