Although conflicting evidence regarding the importance of this signaling pathway in neuronal death has been reported, especially regarding the requirement of GluN2B S1303 phosphorylation by DAPK1 during neuronal death signaling (McQueen et al., 2017; Tullis et al., 2021), the GluN2B-DAPK1 complex has still been well-recognized as one of the critical signaling pathways for NMDAR-receptor mediated excitotoxicity and, consequently, an important drug target for treating ischemic stroke. The gene discussed is GRIN2B; the disease is ischemic stroke.