Importantly, as ERS is associated with sterile inflammatory diseases, such as obesity, type 2 diabetes, Crohn's disease, and cancer (45), and the production of various cytokines, it may be important in the investigation of whether the NLRP3-caspase-8 axis and mitochondrial dysfunction are more intricately engaged with these mechanisms. Here, CASP8 is linked to obesity due to melanocortin 4 receptor deficiency.