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Expanding knowledge of these mechanisms, both in normal physiology and in pathology, identifies targets for potential interventions designed to reduce the complications of renal disease, particularly the cardiovascular sequelae.<jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content>23 has emerged as a major \u03b1\u2010klotho\u2010dependent endocrine regulator of mineral metabolism, functioning to activate vitamin<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>and as a phosphatonin. However, increasingly there is an appreciation that klotho may act independently as a phosphate regulator, as well as having significant activity in other key biological processes. 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