Ingenol mebutate is a substance found in the sap of the plant Euphorbia peplus. Ingenol mebutate gel was developed as a short-course topical therapy for actinic keratosis and non-melanoma skin cancer. It was approved under the trade name Picato by the U.S. Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) for the topical treatment of actinic keratosis in two gel formulations of different strengths for use on either the face and scalp (0.015%) or the trunk and extremities (0.05%). Ingenol mebutate may offer several advantages over other AK treatments currently on the market, including a shorter duration of use, faster resolution of lesions, and a favorable side-effect profile. It was shown in several randomized, double-blind, vehicle-controlled studies that applied topically for 2 to 3 days ingenol mebutate gel is effective for treatment of actinic keratoses. The mechanism of action by which Picato gel induces cell death in treating AK lesions is unknown. It is presumed to involve primary necrosis then neutrophil-mediated inflammation and antibody-dependent cell death of residual disease cells. Also ingenol mebutate activates various protein kinase C (PKC) isoforms, thereby inducing apoptosis in some tumor cells, including myeloid leukemia cells, melanoma cells, and basal cell carcinoma cells. The PKC family consists of signaling isoenzymes that regulate many cell processes including proliferation, differentiation, and apoptosis. Ingenol mebutate (PEP005) has also been found to be useful for reactivating latent HIV virus in cells taken from individuals who have tested negative for signs of the disease following extended courses of anti-retroviral drugs, raising the possibility that this drug may be used to expose the last traces of virus, and thus potentially provide a permanent cure for HIV infection. Research is ongoing to determine whether the effects observed in vitro are also seen in animal models, with a view to eventual human trials for this application.