Complexin 1 and Complexin 2, also designated Synaphin 1 and Synaphin 2, contain an a-helical middle domain of approximately 58 amino acids. Complexin 1 and Complexin 2 are expressed in presynaptic terminals of inhibitory and excitatory hippocampal neurons, respectively, and in cytoplasmic pools during early stages of development. Complexins promote SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) precomplex formation by binding to synaxin with its a-helical domain. Complexins are important regulators of transmitter release at a late step in calcium dependent neurotransmitter release or immediately after the calcium-triggering step of fast synchronous transmitter release and preceding vesicle fusion. Neurons lacking complexins show reduced transmitter release efficiency due to decreased calcium sensitivity of the synaptic secretion process. Complexin 2 may play a role in LTP (long term potentiation) following tetanic stimulation. A progressive loss of Complexin 2 occurs in the brains of mice carrying the Huntington disease mutation, an autosomal dominant neurodegenerative disorder. Changes in the neurotransmitter release might contribute to the motor, emotional and cognitive dysfunctions seen in these mice.