Vesicular glutamate transporter (VGLUT) is responsible for the active transport of L-glutamate into synaptic vesicles and, thus, plays an essential role in the glutamatergic chemical transmission in the central and peripheral nervous systems. Recent studies indicated that VGLUT is also expressed and localized in various secretory vesicles in non-neuronal peripheral organelles such as hormone-containing secretory granules in endocrine cells. L-Glutamate is stored in VGLUT-containing organelles, secreted upon stimulation, and then acts as a paracrine and/or autocrine modulator to regulate cellular functions. Thus, VGLUT is a key molecule for glutamate signaling and is the core of a novel signaling system.