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Obesity and hyperlipidemia are the most prevalent independent risk factors of ESRD, suggesting that lipid accumulation is detrimental to renal function. The origin of lipid accumulation (a common feature in podocyte injury) and its pathophysiological relevance are unknown. This commentary discusses the finding by Liu et al. that deficiency of the endoplasmic reticulum enzyme SOAT1, which metabolizes cholesterol to cholesterol esters, attenuates renal/podocyte injury in murine models of diabetes and Alport's syndrome.Gain-of-function var