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Uridine (U) is a remarkably important molecule that is essential for a number of evolutionary and biological processes. It consists of the pyrimidine-analog uracil, which is linked to a ribose sugar. Uracil itself can be formed abiotically from pyrimidine, suggesting that this base is a central building block of life. Uridine, by contrast, is a precursor for RNA, thus linking genetic information to the expression of proteins. Importantly, when phosphorylated to uridine triphosphate (UTP), it activates glucose to synthesize glycogen stores and thereby controls glucose metabolism. Uridine also has been implicated in neuron functions and brain processes. On page 1173 of this issue, Deng et al. (1) offer transformative insights into the systemic regulation of circulating uridine and its actions in mammals, with implications for the potential of therapeutic uridine supplementation in general and new precision treatments of metabolic diseases in particular.