AIM: To study the function of N-copine on cell level by investigating the effect of N-copine antisense on the cultured cortical neuron of mouse embryos. METHODS: Neuronal cultures were prepared from cerebral cortices of 16-day old mouse (BALB/C) embryos. N-copine expression was blocked by using antisense oligonucleotides. The effect of inhibition of N-copine expression on the cultured neuronal viability and development was observed. RESULTS: With oligonucleotides treatment for 72 h, the length of neuronal axon and the area of neurosoma in antisense group were decreased markedly as compared with those in control group. The number of trypan-blue-stained neurons and the LDH activity of the culture media were increased significantly as compared with those in control groups. CONCLUSIONS: Inhibition of N-copine expression affects the development of cortical neuron cultured in vitro, and induces the neuron demaged severely. The results suggest that N-copine is a functional protein in neurons, and it may play an important role in the regeneration of nervous system and preventing neuronal degeneration.