Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The enzyme ectonucleotide pyrophosphatase/phosphodiesterase 1 () codes for a type 2 transmembrane glycoprotein that hydrolyzes extracellular ATP to generate pyrophosphate (PP) and adenosine monophosphate, thereby contributing to downstream purinergic signaling pathways. The clinical phenotypes induced by ENPP1 deficiency are seemingly contradictory and include early-onset osteoporosis in middle-aged adults and life-threatening vascular calcifications in the large arteries of infants with generalized arterial calcification of infancy. The progressive overmineralization of soft tissue and concurrent undermineralization of skeleton also occur in the general medical population, where it is referred to as paradoxical mineralization to highlight the confusing pathophysiology. This review summarizes the clinical presentation and pathophysiology of paradoxical mineralization unveiled by ENPP1 deficiency and the bench-to-bedside development of a novel ENPP1 biologics designed to treat mineralization disorders in the rare disease and general medical population.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062289 | PMC |
| http://dx.doi.org/10.1146/annurev-pathmechdis-051222-121126 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Kinetic mechanism of ENPP1 ATPase: Implications for aberrant calcification disorders and enzyme replacement therapy.
J Biol Chem
August 2025
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA. Electronic address:
Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) is a transmembrane glycoprotein enzyme with an extracellular catalytic domain that hydrolyzes ATP into AMP and pyrophosphate (PP). The ENPP1 ATPase is the major source of extracellular PP, a critical physiological regulator of calcium phosphate crystal formation and biomineralization. ENPP1 deficiency lowers systemic PP levels and induces life-threatening arterial calcifications.
View Article and Find Full Text PDFImprovements in hearing loss with bone-targeted enzyme replacement therapy are associated with corrected hypomineralization and osteocyte properties of auditory ossicles in Enpp1-deficient mice.
J Bone Miner Res
August 2025
Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, United States.
Hearing loss is common in conditions caused by ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) deficiency, such as generalized arterial calcification of infancy and autosomal recessive hypophosphatemic rickets type 2. Mechanistically, it is hypothesized that poor mineralization of the auditory ossicles leads to impaired sound transmission in the middle ear. Here we investigated whether enzyme replacement therapy (ERT) improves hearing loss in an Enpp1-deficient mouse model and whether this is associated with corrected bone properties in the ossicles.
View Article and Find Full Text PDFPhenotypic characterization of ENPP1 deficiency: generalized arterial calcification of infancy and autosomal recessive hypophosphatemic rickets type 2.
JBMR Plus
May 2025
Department of General Pediatrics, Münster University Children's Hospital, 48149 Münster, Germany.
Generalized arterial calcification of infancy (GACI) and autosomal recessive hypophosphatemic rickets type 2 (ARHR2) are age-related phenotypes of the rare genetic mineralization disorder, ENPP1 Deficiency, which evolve on a phenotypic continuum. To date, our understanding of the clinical spectrum of ENPP1 Deficiency is based on small studies or case reports, across which there is significant variability in clinical presentation, and limited duration of follow-up. From a previously published large retrospective natural history study, we performed a subgroup analysis to elucidate the most prevalent signs and symptoms of ENPP1 Deficiency diagnosed as GACI or ARHR2, to illustrate the onset and incidence of these complications over the lifetime, and to characterize the associated medical burden of disease.
View Article and Find Full Text PDFEnpp1 ameliorates MAFLD by regulating hepatocyte lipid metabolism through the AMPK/PPARα signaling pathway.
Cell Biosci
February 2025
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical College (PUMC), Beijing, 100021, China.
Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) has become the leading chronic liver disease globally, and there are no approved pharmacotherapies to treat this disease. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) has been found to be related to insulin resistance and lipid accumulation. However, the role and mechanism of Enpp1 in the development of MAFLD remain unknown.
View Article and Find Full Text PDFBase of Skull & Spinal Canal Narrowing in an Adolescent with Autosomal Recessive Hypophosphatemic Rickets Type 2.
Calcif Tissue Int
January 2025
Department of Paediatric Endocrinology, Alder Hey Children's Hospital, Liverpool, UK.
Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) is an uncommon hereditary form of rickets characterised by chronic renal phosphate loss and impaired bone mineralisation. This results from compound heterozygous or homozygous pathogenic variants in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), a key producer of extracellular inorganic pyrophosphate (PPi) and an inhibitor of fibroblast growth factor23 (FGF23). ENPP1 deficiency impacts FGF23 and increases its activity.
View Article and Find Full Text PDF