Maintenance of reduction–oxidation equilibrium is important to protect cells from oxidant damage and to initiate damage repair. Nucleoredoxin (NXN) is a thioredoxin that can regulate cellular redox homeostasis. It interacts with multiple proteins to regulate several pathways, including disheveled (DVL), a key component of the WNT signaling pathway. In the presence of reactive oxygen species, the cysteine residues of NXN are reduced, which results in the release of DVL that can decrease or increase WNT signaling.

Biallelic mutations in NXN are a rare cause of Robinow Syndrome, which is characterized by short stature, skeletal dysplasia that includes mesomelic limb shortening, and mild facial dysmorphology. Some Robinow syndrome cases are associated with cleft lip and/or cleft palate. Interstingly, Robinow syndrome can also be caused by mutations in other genes that are important in the WNT signaling pathway. In their new study titled "Nucleoredoxin regulates WNT signaling during pituitary stem cell differentiation", Dr. Shannon Davis' lab and their collaborators at the University of Michigan report that Nxn is expressed in the ventral diencephalon and developing pituitary gland, and that Nxn deficient mice have pituitary dysmorphology and craniofacial abnormalities that include defects in the skull base and cleft palate. Nxn mutant mice also exhibit reduced WNT signaling and reduced differentiation of pituitary stem cells into hormone-producing cells. Altogether, these results suggest that patients with Robinow syndrome could benefit from evaluation by endocrinologists for pituitary structural imaging and hormone insufficiency.