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Abstract Purpose Unlike treatment with high doses of radiation that causes considerable DNA damage resulting in injury and p53 activation, exposure of cells or whole animals to low doses of radiation (LDR, ∼10cGy) can induce a protective radio adaptive response. Despite ample information about the contribution of the p53 pathway to high doses of radiation-induced effects, our understanding of the role of p53 in LDR-induced response remains incomplete. This review provides a brief summary of the p53 response to LDR exposure focusing on metabolic regulation. Conclusion Consistent with growing evidence indicating a critical role of metabolic pathways in the modulation of stress responses, the radio adaptive response was mediated by the LDR-induced metabolic switch from oxidative phosphorylation to glycolysis. Remarkably, this metabolic reprogramming depends on p53 downregulation, suggesting a previously unrecognized p53-mediated metabolic response. Of note is that the LDR-induced p53 response is temporary but may become persistent if LDR exposure is recurrent and protracted. While further investigation is necessary, the model where LDR induces p53 downregulation concurrent with anabolic reprogramming may offer novel mechanistic insight into the radio adaptive response. It suggests a model in which LDR exposure is protective when transient or intermittent but may become detrimental when chronic because prolonged p53 downregulation would lead to inactivation of this critical tumor suppressor, causing a loss of p53-dependent DNA damage checkpoint, genomic instability, dysregulated metabolism, and thus increased cancer risk.