Magnesium transporter NIPA4 (NIPAL4)

NIPAL4 (Magnesium transporter NIPA4) is a transmembrane protein with nine helices, predominantly expressed in the granular layer of the epidermis. It primarily acts as a magnesium transporter, but also facilitates the transport of other divalent cations. NIPAL4 is central to epidermal lipid metabolism by participating in the synthesis of very long chain fatty acids and the formation/secretion of lamellar bodies, thus maintaining the integrity of the skin barrier. Pathogenic mutations in NIPAL4 are the second most common genetic cause of autosomal recessive congenital ichthyosis (ARCI), leading to abnormal lipid composition and barrier dysfunction characteristic of this disease. There is no clear evidence for approved drugs directly modulating NIPAL4, but molecular and cellular studies suggest that restoring skin lipid homeostasis, e.g., via retinoid mimetics, can partly compensate for its deficiency

Other names

NIPAL4NIPA-like domain containing 4Magnesium transporter NIPA4IchthyinARCI6ICHTHYINICHYNSLC57A6Non-imprinted in Prader-Willi/Angelman syndrome region protein 4

Not established for drug targeting; ARCI symptoms can be partially ameliorated by retinoid-mimetic treatment, suggesting impact via restoration of epidermal lipid metabolism