The epidermal permeability barrier is established late in fetal development. Indeed, the Ca(2+) gradient is crucial to the normal development of skin. Human epidermis displays a characteristic calcium gradient, with lower calcium levels in the basal and spinous layers, which increases progressively towards the outer SG. The distribution pattern of ionic calcium correlates with growth and differentiation of keratinocytes, as low extracellular calcium concentrations stimulate the growth of keratinocytes with high proliferation rate, and a high extracellular calcium levels induce differentiation and stratification. The Ca(2+) gradient has been shown to regulate lamellar body secretion independent of barrier formation. Such gradient is not observed in skin abnormalities related to the formation of abnormal barrier function (e.g. atopic dermatitis and psoriasis) and acute disruption of the epidermal permeability barrier, which causes an influx of water into stratum corneum and immediate loss of calcium gradient. The depletion of calcium gradient regulates lamellar body exocytosis which restoration appears in parallel with barrier recovery. Therefore, the regulation of calcium gradient in epidermis is essential to maintain the skin barrier function and to avoid dry skin.