Our study showed the regulatory effect of mTOR–Akt on ERS–UPR in a murine CLP model by analyzing the proteins of the mTOR–Akt–ERS signaling pathway, and suggested that mTOR–Akt–IRE1α–JNK signaling has the potential to serve as a clinical immunotherapy target for sepsis and provide a new direction for sepsis immunotherapy. Here, AKT1 is linked to Sepsis.