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Up to one in four people may be at risk of premature death or disability as a consequence of the symptoms associated with metabolic syndrome. In this Special Issue of The Journal of Physiology, a series of invited reviews examine the role that AMP-activated protein kinase (AMPK) might play in the regulation of the body's energy status in health - from the cellular control of metabolism in rest and exercise, through to the control of feeding - and in disease, where putative roles for this enzyme in diabetes, hepatic and respiratory disease as well as cancer and atherosclerosis have been proposed. (Image kindly supplied by Dr Prem Kumar.)