TYR and freckles: It is postulated that solar lentigines (SLs), hyper-pigmentary spots on sun-exposed skin of aged persons, could be treated by combined topical treatment with EDN signaling blockers and tyrosinase inhibitors [22], and SCF inhibitors or EDN1-triggered intracellular signaling cascades can downregulate the hyperpigmentation observed in solar lentigo, UVB (ultraviolet ray-B) induced melanosis, and melasma [23].