More importantly, we have provided compelling evidence that SENP6 functions as an isopeptidase to deconjugate SUMO from ANXA1, thereby facilitating ANXA1 translocation to the nucleus, activating the caspase-3 apoptosis pathway and inducing neuronal apoptotic death after cerebral ischemia-reperfusion injury (Figure 9). The gene discussed is ANXA1; the disease is brain ischemia.