Abstract: Objective To explore the change of Cpne5 protein expression during SH-SY5Y cell apoptosis. Methods The models of A23187 or serum-deprivation inducing SH-SY5Y cells apoptosis were used, and the morphology observation and apoptosis rate were detected by flow cytometry. The changes of Cpne5 protein expression during two processes were detected by western blotting. Results After induced by A23187 (10μmol/L) for 24 hours, SH-SY5Y cells were shrinked and its apoptotic rate was rose. The expression of Cpne5 protein was significantly increased from 0.5 h to 12 h after SH-SY5Y cells treated by A23187, and then reduced to the pre-induced level at 24h. The apoptosis rate of 24 samples of SH-SY5Y cells was 23.2±2.1% after 72 h serum-deprivation; it was significantly higher than that of controls (1.1±0.1%). There was no significant change on Cpne5 protein expression when SH-SY5Y cells were treated with serum-deprivation at 1, 6, 12, 24, and 72h.  Conclusion Cpne5 protein expression was significantly changed in early apoptosis of SH-SY5Y cells when induced by A23187. The Cpne5 gene may be involved in regulation of apoptosis by calcium signaling pathways.