Synaptotagmin 1 (SYT1) acts as a calcium sensor to mediate synchronous calcium-triggered synaptic vesicle exocytosis in neurons. Syt1 deletion in forebrain neurons prevents such transmission and reveals a slower form of neurotransmitter release — asynchronous release — for which the calcium sensor has been unclear. Bacaj et al. show that hippocampal neurons express two calcium-binding SYTs — SYT1 and SYT7 — and that loss of SYT7 in SYT1-deficient neurons suppresses asynchronous release. This could be rescued by SYT7 expression, indicating that SYT7 may act as the second calcium sensor in these neurons.