The NIPA family is currently comprised of 4 members- NIPA1-4. These members have a molecular similarity of 40%. NIPA proteins are integral membrane proteins which function as Mg²⁺ transporters.

The NIPA4 gene in mice is located on chromosome 11B1.1 and the human corresponding gene, hIchthyin is located on chromosome 5q33.3. Both genes share an 85% amino acid similarity. Interestingly, NIPA2-4 show greater common identity in their ancestral invertebrate polypeptides than they do to NIPA1 suggesting different physiological roles. NIPA4 mediates Mg²⁺ uptake with a Km of 0.36 mM but unlike NIPA2, which is selective for Mg²⁺, it has been found to transport other cations as well.

Mutations in the hIchthyin gene provide the basis of one form of autosomal-recessive congenital ichthyosis (ARCI). ARCI is a heterogenous group of disorders with abnormal differentiation and desquamation of the epidermis, leading to widespread scaling and erythema of the skin. To this day six homozygous mutations have been found, including one nonsense and five missense mutations, in a large number of consanguineous families presenting with ichthyosis. The function of ichthyin in skin differentiation is not fully understood but it has been suggested that because lipid dysfunctions are involved with the other ARCI disorders ichthyin might perform as a membrane receptor for trioxilins of the hepoxilin pathway.

Although some NIPA proteins have been implicated as candidates for prader-willi syndrome their involvement remains unclear. Currently there is no evidence that NIPA4 is directly involved in the many complexities of the syndrome¹.