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. In mammals, Bpnt1, along with Golgi-resident PAP phosphatase (gPAPP), hydrolyzes 3'-phosphoadenosine 5'-phosphate (PAP) to 5'-AMP, a process crucial for normal physiological function [1,2,3].

Mice lacking Bpnt1 develop iron-deficiency anemia, anasarca, and severe liver pathologies including hypoproteinemia, hepatocellular damage, and in severe cases, whole-body edema and death [1,3]. The loss of Bpnt1 leads to PAP accumulation in tissues like the liver, duodenum, and kidneys, resulting in aberrant nucleolar architecture and repressed translation [2,3]. Additionally, intestinal-epithelium specific loss of Bpnt1 attenuates hepatic iron accumulation in mice with homozygous C282Y mutations in homeostatic iron regulator (HFEC282Y), suggesting its potential in hemochromatosis treatment [1]. In Caenorhabditis elegans, loss of bpnt-1 function suppresses lethality caused by paxt-1 deletion through XRN2 autoregulation [4].

In conclusion, Bpnt1 is vital for sulfur assimilation metabolism, and its deficiency causes multiple physiological defects. The Bpnt1 knockout mouse models have revealed its role in iron homeostasis, liver function, and potential in treating diseases like hemochromatosis. These findings contribute to understanding the underlying mechanisms of related diseases and may offer new therapeutic targets.