Bpnt1, also known as bisphosphate 3'-nucleotidase 1, is a key regulator in the sulfur assimilation metabolic pathway. This pathway is essential for sulfation, amino acid metabolism, nucleotide hydrolysis, and maintaining organismal homeostasis [1,2,3,4]. In mammals, Bpnt1, along with Golgi-resident PAP phosphatase (gPAPP), is involved in hydrolyzing 3'-phosphoadenosine 5'-phosphate (PAP) to 5'-AMP [2,3].

Mice lacking Bpnt1 develop iron-deficiency anemia, anasarca, and severe liver pathologies such as hypoproteinemia, hepatocellular damage, and in severe cases, whole-body edema and death [1,3]. The loss of Bpnt1 leads to the accumulation of PAP in tissues like the liver, duodenum, and kidneys, causing aberrant nucleolar architecture and liver failure [2,3]. However, these phenotypes can be rescued by dietary methionine restriction, overproduction of hypoxia inducible factor 2α (Hif-2a), or genetically repressing PAPS synthesis [1]. In Caenorhabditis elegans, loss of bpnt-1 function suppresses lethality caused by paxt-1 deletion through XRN2 autoregulation [5].

In conclusion, Bpnt1 is crucial for maintaining normal physiological functions, especially in sulfur assimilation, iron homeostasis, and hepatic function. The study of Bpnt1 knockout mouse models has revealed its significant role in diseases such as anemia and hemochromatosis, providing potential therapeutic targets for these conditions [1].