ERN1 and obesity due to melanocortin 4 receptor deficiency: It is known that PKA-mediated phosphorylation of its substrate causes lipolysis in cancer and obesity (Djouder et al., 2010), and one such substrate proposed recently is IRE1, where it is shown that phosphorylation of IRE1 by PKA (other than itself) up-regulates gluconeogenic genes and, thus, promotes hyperglycemia and glucose intolerance in obese mice (Mao et al., 2011).