iRhom2 is a polytopic membrane protein that is highly expressed in immune cells, particularly macrophages. iRhom2 is required for the release of tumor necrosis factor (TNF) from myeloid cells. TNF, in turn, regulates the pathobiology of metabolic syndrome in several important ways. Badenes et al. evaluated the contribution of iRhom2 to metabolic syndrome. They report that iRhom2 knockout mice are protected from a range of deleterious metabolic phenotypes including obesity, adipose tissue inflammation, hepatic steatosis, and insulin resistance. Moreover, loss of iRhom2 enhances the capacity of the animals to dissipate excess energy via increased thermogenesis.