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

The enzyme ectonucleotide pyrophosphatase phosphodiesterase 1 ( ENPP1 ) codes for a type 2 transmembrane glycoprotein that hydrolyzes extracellular ATP to generate pyrophosphate (PP i ) and adenosine monophosphate, thereby contributing to downstream purinergic signaling pathways. The clinical phenot...

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Bibliographic Details
Published in:Annual review of pathology 2024-01, Vol.19 (1), p.507-540
Main Authors: Ferreira, Carlos R, Carpenter, Thomas O, Braddock, Demetrios T
Format: Article
Language:English
Subjects:
Adult
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
Humans
Middle Aged
OPLL
ossification of the posterior longitudinal ligament
Phosphoric Diester Hydrolases - genetics
Phosphoric Diester Hydrolases - metabolism
pseudoxanthoma elasticum
PXE
Pyrophosphatases - genetics
Pyrophosphatases - metabolism
Vascular Calcification - drug therapy
Vascular Calcification - genetics
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Summary:The enzyme ectonucleotide pyrophosphatase phosphodiesterase 1 ( ENPP1 ) codes for a type 2 transmembrane glycoprotein that hydrolyzes extracellular ATP to generate pyrophosphate (PP i ) 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.
ISSN:1553-4006
1553-4014
DOI:10.1146/annurev-pathmechdis-051222-121126