The 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 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.

中文翻译：

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血液和骨骼中的 ENPP1：ENPP1 缺乏引起的骨骼和软组织疾病


胞外核苷酸焦磷酸酶/磷酸二酯酶 1 (ENPP1) 编码 2 型跨膜糖蛋白，可水解细胞外 ATP 生成焦磷酸 (PPi) 和单磷酸腺苷，从而促进下游嘌呤能信号通路。 ENPP1缺乏引起的临床表型看似矛盾，包括中年成人早发性骨质疏松症和婴儿大动脉危及生命的血管钙化（婴儿期全身动脉钙化）。软组织进行性过度矿化和同时发生的骨骼破坏也发生在普通医学人群中，被称为矛盾矿化以突出令人困惑的病理生理学。本综述总结了 ENPP1 缺乏所揭示的矛盾矿化的临床表现和病理生理学，以及旨在治疗罕见疾病和普通医学人群矿化障碍的新型 ENPP1 生物制剂的实验室到临床开发。