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Rottlerin is a natural polyphenolic compound, which was initially indicated and marketed as a PKC δ inhibitor and recently proposed and patented as an anti-hypertensive drug. In vitro results from our Laboratory and data from the literature suggest a potential use of Rottlerin in the treatment/control of psoriasis, a skin disease characterized by abnormal cellular proliferation, abnormal angiogenesis and inflammation. Rottlerin, indeed, is an antioxidant and a potent inhibitor of the transcription factor NFκB, a key mediator of immune responses and a crucial regulator of cell cycle and apoptosis in immune cells, endothelial cells and keratinocytes. Herein, we will review the multiple activities of Rottlerin (antioxidant, antiproliferative, antiangiogenic and anti-inflammatory) that give to the drug the potential to be used as a new therapeutic approach against psoriasis.