Nrdp1 is inducible in cells in response to different stimuli, and its stability largely relies on its substrate USP8, a de-ubiquitinating enzyme (Wu et al., 2004). Thus, Nrdp1 and USP8 may restrict each other (De Ceuninck et al., 2013). When Nrdp1 is increased, more USP8 will be degraded by Nrdp1, and as a return, less USP8 will make Nrdp1 unstable, resulting in less Nrdp1 and more USP8 in the cells. Consistently, here our data also show that under OGD condition, Nrdp1 upregulation concurrently occurs with USB8 downregulation in neuronal cells. Moreover, Nrdp1 overexpression augments OGD-induced USP8 downregulation, while knockdown of Nrdp1 ameliorates this effect. Although we did not design experiments to verify USP8’s effect in stabilizing Nrdp1 protein in neurons under ischemic conditions, our data clearly demonstrate that the interaction between these two proteins is associated with OGD-induced neuronal death.