Rhomboid pseudoproteases: An Achilles heel's for BCL-2/IP3R-dependent resistance to ER stress-induced cell death

Anti-apoptotic BCL-2 targets and inhibits IP3 receptors (IP3Rs), thereby preventing apoptosis by limiting ERmitochondrial Ca2+ flux. Recently, Dulloo et al. (2022), Nat. Comm. 13:1257[6] revealed a novel role for rhomboid pseudoproteases in ER stress-induced apoptosis by stripping BCL-2 from IP(3)Rs, thereby enabling pro-apoptotic Ca2+ signaling.