Future studies will have to specifically examine the role of the myeloid-specific deletion of S100A8/A9, particularly S100A8 in the pathogenesis of sepsis-induced hepatic dysfunction, define the precise mechanism by which S100A8/A9 inhibits the activation of AMPK signaling in the liver, and determine whether targeting S100A9 presents a new opportunity for the treatment of sepsis and multiple organ failure. The gene discussed is PRKAA1; the disease is Sepsis.