Neurotransmitter release is critical for maintaining normal organism function, it is mediated by the vesicle transportation. A bundle of proteins regulate the complicated neuronal vesicle transmission by interacting with each other. The small soluble protein Complexin (Cpx) plays an important role that can both inhibit spontaneous vesicle fusion and promote evoked Ca²⁺-dependent neurotransmitter release. In this review, we highlight the recent advances in the function of each domain of Cpx and the mechanisms of interacting with other vesicle exocytosis associated proteins such as SNARE complex and synaptotagmin.