In neuronal cells, smooth endoplasmic reticulum (SER) is a key component of the neuronal signaling process. SER is distributed throughout neurons, and it represents the principal site for the storage and release of the intracellular second messenger, calcium. As the primary site of Ca2+ release, as well as of Ca2+ uptake, the SER regulates the local cytosolic Ca2+ concentration and hence the coupling of electrical excitation to the activation of signal transduction cascades. To perform these functions, the SER must be positioned at the proper location within the cell, which, in the case of neurons, is the dendritic spines (Fig. 1⇓), the sites of synaptic input to postsynaptic neurons. For example, in the dendritic spines of cerebellar Purkinje cells, excitation leads to Ca2+ influx through voltage-sensitive Ca2+ channels. This small influx triggers Ca2+-induced release of calcium from the SER via ryanodine receptors. In addition, excitation via metabotropic glutamate receptors leads to the production of inositol 1,4,5-trisphosphate (IP3), which causes the release of Ca2+ from the SER through IP3 receptors. By these mechanisms, Ca2+ is thought to initiate the cellular mechanisms that lead—among other functions—to learning and memory appropriate to the neuron in question.