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 缺陷诱导的骨骼和软组织疾病


外核苷酸焦磷酸酶/磷酸二酯酶 1 （ENPP1） 编码一种 2 型跨膜糖蛋白，该糖蛋白水解细胞外 ATP 生成焦磷酸盐 （PPi） 和腺苷一磷酸盐，从而有助于下游嘌呤能信号通路。ENPP1 缺乏症诱导的临床表型看似矛盾，包括中年人早发性骨质疏松症和婴儿全身性动脉钙化婴儿大动脉危及生命的血管钙化。软组织的进行性过度矿化和骨骼的矿化不足也发生在一般医学人群中，它被称为反常矿化，以突出令人困惑的病理生理学。本文总结了 ENPP1 缺陷揭示的反常矿化的临床表现和病理生理学，以及一种新型 ENPP1 生物制剂的从实验室到床边开发，旨在治疗罕见病和一般医学人群的矿化障碍。