The Ca²⁺-dependent precursor convertase furin is abundantly expressed in epidermal keratinocytes and melanocytes. In this context it is noteworthy that proopiomelanocortin (POMC) cleavage is also processed by furin leading to ACTH, -LPH, and -endorphin. All prohormone convertases including furin are regulated by Ca². Since numerous epidermal peptides and enzymes are affected by H₂O₂-mediated oxidation, including the POMC derived peptides -MSH and -endorphin as shown in the epidermis of patients with vitiligo, we here asked the question whether furin could also be a possible target for this oxidation mechanism by using immunofluorescence, RT-PCR, Western blotting, Ca²⁺ binding studies, and computer modelling. Our results demonstrate significantly decreased in situ immunoreactivity of furin in the epidermis of patients with progressive vitiligo (n=10) suggesting H₂O₂-mediated oxidation. This was confirmed by [⁴⁵Ca²⁺] binding studies with human recombinant furin identifying the loss of one Ca²⁺-binding site from the enzyme after oxidation with H₂O₂. Computer simulation supported alteration of one of the two Ca²⁺-binding sites on furin. Taken together, our results implicate that the Ca²⁺ dependent proteolytic activity of this convertase is targeted by H₂O₂ which in turn could contribute to the reduced epidermal expression of the POMC-derived peptides -MSH and -endorphin as documented earlier in patients with vitiligo.