Neuregulin receptor degradation protein-1 (Nrdp1, also known as FLRF or RNF41), is a ring finger E3 ubiquitin ligase and primarily expressed in the brain, heart, prostate and skeletal muscle (Diamonti et al., 2002). Several studies have demonstrated an important role of Nrdp1 in regulating cell growth, apoptosis, oxidative stress and inflammation, in which Nrdp1 promotes the ubiquitination of ubiquitin-specific protease 8 (USP8), ErbB3, ErbB4, BRUCE/Apollon, MyD88 and Parkin (Qiu et al., 2004; Yen et al., 2006; Yu and Zhou, 2008; Wang et al., 2009; De Ceuninck et al., 2013; Sun et al., 2017). In a previous study, we have shown that Nrdp1 is implicated in ischemic cardiomyocyte death, in which overexpression of Nrdp1 augmented ischemia–reperfusion (I/R)-induced cardiomyocyte apoptosis while inhibition of endogenous Nrdp1 could protect cardiomyocytes against I/R injury (Zhang et al., 2011b). In the brain, Nrdp1 is found to be involved in suppressing brain tumor formation and promoting lipopolysaccharide (LPS)-induced neuroinflammation via its pro-apoptotic action (Shen et al., 2015; Shi et al., 2015; Wu et al., 2016). It is well known that neuronal apoptosis is a major event in ischemic stroke, however, the role of Nrdp1 in ischemic neuronal death has not yet been investigated. Our preliminary data shows that cerebral ischemia induces Nrdp1 mRNA expression in ischemic cerebral cortex in a rat model of middle cerebral artery occlusion (MCAO). However, the exact role of Nrdp1 in ischemia-induced neuronal damage remains to be determined.