Moreover, the upregulation of ion-exchange regulatory protein PDZ domain-containing kidney 1 (PDZK1) in melasma lesions has been found to potentially facilitating interactions between oestrogen signalling and ion transport mechanisms that promote melanogenesis and melanosome transfer.39,49,50 It was also postulated that oestrogen contributed to keratinocyte growth factor (KGF) production which affects melanocyte proliferation, tyrosinase activity and melanosome transfer ultimately resulting in melasma.34,51. This evidence concerns the gene PDZK1 and freckles.