Diverse roles of Synaptotagmin-7 in regulating vesicle fusion

•Syt7 is a Ca sensor for facilitation, asynchronous release, and replenishment.•Facilitation by Syt7 can allow depressing synapses to be frequency invariant.•Syt7 can suppress spontaneous vesicle fusion.•Ca, temperature, other Syts, and location influence Syt7’s effect on transmission. Synaptotagmin 7 (Syt7) is a multifunctional calcium sensor expressed throughout the body. Its high calcium affinity makes it well suited to act in processes triggered by modest calcium increases within cells. In synaptic transmission, Syt7 has been shown to mediate asynchronous neurotransmitter release, facilitation, and vesicle replenishment. In this review we provide an update on recent developments, and the newly emerging roles of Syt7 in frequency invariant synaptic transmission and in suppressing spontaneous release. Additionally, we discuss Syt7’s regulation of membrane fusion in non-neuronal cells, and its involvement in disease. How such diversity of functions is regulated remains an open question. We discuss several potential factors including temperature, presynaptic calcium signals, the localization of Syt7, and its interaction with other Syt isoforms.