In humans, there are 48 members of the superfamily of nuclear receptors. These ligand-activated transcription factors help to integrate our growth, reproduction and metabolism via environmental, nutritional and intrinsic cues. It is therefore not surprising that nuclear receptors are commonly used as drug targets. However, perhaps in the rush to discover new drugs that target these receptors, we sometimes lose sight of their ‘real’ physiological ligands. In this issue of the Biochemical Journal Goto et al. present evidence that the isoprenoid FPP (farnesyl pyrophosphate) may be a bona fide ligand for the master controller of adipocyte differentiation PPARγ (peroxisome-proliferator-activated receptor γ). This work has wide-ranging implications not only for obesity and diabetes, but also for osteoporosis and the control of circadian rhythms in which PPARγ also plays an important role.

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