Background: AMP-activated protein kinase (AMPK) is a serine/threonine kinase which improves symptoms of the metabolic syndrome. Cereblon (CRBN) is a negative regulator of AMPK, and known as a target protein of mental retardation, T cell immunomodulation, and anti-proliferative action of thalidomide. Recently, it has been known to have anti-obesity and cardioprotective effect, but there is no study of the influence of CRBN changes on skin. Objectives: We investigated the role of CRBN of skin by comparing CRBN gene knockout (CRBN-KO) with wild type (WT) mice by ultraviolet (UV) irradiation. Methods: Twelve CRBN-KO, twelve WT were tested and half were irradiated with a certain amount of (UV) irradiation everyday for 14 weeks. Skin erythema, pigmentation were measured using a Dermavision® and skin barrier function by tewameter and corneometer. After final UV irradiation, skin biopsy was done to figure out morphology change. Results: After UV irradiation, CRBN-KO have tendency to increase TWEL, erythema and decrease pigmentation, collagen fiber, elastic fiber, extracellular matrix, and subcutaneous fat more slightly but there was no significant difference between the two groups. SCH decreased in both groups, but WT decreased more significantly. Conclusion: Based on the results of the present study, CRBN may affect the aging of the skin by reduction of structural network. We expect that the role of CRBN in the skin will be clarified.