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Annual Review of Pathology: Mechanisms of Disease

Volume 19, 2024

ENPP1 in Blood and Bone: Skeletal and Soft Tissue Diseases Induced by ENPP1 Deficiency

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.

Keyword(s): ARHR2, autosomal recessive hypophosphatemic rickets type 2, DISH, dystrophic idiopathic spinal hyperostosis, ectonucleotide pyrophosphatase/phosphodiesterase 1, ENPP1 deficiency, enthesopathy, GACI, generalized arterial calcification of infancy, OPLL, ossification of the posterior longitudinal ligament, pseudoxanthoma elasticum, PXE
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/content/journals/10.1146/annurev-pathmechdis-051222-121126
2024-01-24
2024-04-29
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/content/journals/10.1146/annurev-pathmechdis-051222-121126
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ENPP1 in Blood and Bone: Skeletal and Soft Tissue Diseases Induced by ENPP1 Deficiency
Annual Review of Pathology: Mechanisms of Disease 19, 507 (2024); https://doi.org/10.1146/annurev-pathmechdis-051222-121126
/content/journals/10.1146/annurev-pathmechdis-051222-121126
/content/journals/10.1146/annurev-pathmechdis-051222-121126
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