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Over transferrin bound (TBI) and non-transferrin bound iron (NTBI) can overwhelm the heavy chain ferritin (FtH) capacity, which lead to release of labile iron and render proximal tubular epithelial cells (PTEC) susceptible to iron oxidant damage, especial in distal tubular epithelial cells (DTEC) with lack iron storage (light and heavy chain ferritin) and export protein (ferroportin) (48)

However, if the toxic or injurious insult persists, GCLC expression may become dysregulated

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For example, zinc and vitamin D are often low in people with depression

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