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

Annu Rev Pathol. 2023 Oct 23. doi: 10.1146/annurev-pathmechdis-051222-121126. Online ahead of print.ABSTRACTThe enzyme ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) codes for a type 2 transmembrane glycoprotein that hydrolyzes extracellular ATP to generate pyrophosphate (PPi) 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 occurs 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. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 19 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.PMID:37871131 | DOI:10.1146/annurev-pathmechdis-051222-121126
Source: Annual Review of Pathology - Category: Pathology Authors: Source Type: research