TP53 and ischemia: Similarly, in ischemia, MANF plays a role in curbing neuronal apoptosis by orchestrating UPR-related genes (such as GRP78, phosphorylated IRE1, and XBP1s) (Yang et al. 2014b) and activating the Akt/MDM2/P53 pathway (Airavaara et al. 2009; Zhao et al. 2013).