In the setting of ER stress the three trans-membrane biosensors PERK, ATF6, and IRE1-a are activated. PERK activation induces the expression of the proapoptotic transcription factor CHOP. CHOP in turn, mediates apoptosis through several pathways including generation of ROS. IRE1-a activates JNK a key player in apoptosis. IRE1-a also generates a spliced form of XBP (s-XBP) that promotes degradation of misfolded proteins. ATF6 contributes in CHOP induction, and heterodimerizes with XBP, enhancing protein degradation.