细胞外基质（ECM）的矿化是生理性骨形成和病理性钙化的重要过程。ECM矿化异常功能导致全球发展矿化相关疾病的风险增加；例如，血管钙化归因于ECM矿化的高功能，而骨质疏松症由低功能引起。骨化囊膜蛋白A6（AnxA6）是一种钙依赖的磷脂结合蛋白，在骨质疏松症、骨关节炎、动脉粥样硬化、骨肉瘤和钙化主动脉瓣病等矿化相关疾病中被广泛报道为重要靶点。截至目前，作为Annexin家族中最大的成员，AnxA6因其在基质囊泡（MVs）的产生与释放、MVs-ECM相互作用、胞浆Ca2+流入和羟磷灰石成熟等方面的显著贡献而备受关注，使其成为ECM矿化的重要靶点。在本综述中，我们概述了AnxA6在矿化相关疾病中的作用以及在正常和矿化相关病理条件下的潜在机制的最新进展。AnxA6可以促进ECM矿化，以先前描述的方式实现骨再生。因此，AnxA6可能是ECM矿化的潜在造骨靶点。版权所有© 2023 Yang, Pei, Su, Duan and Liu.

The mineralization of the extracellular matrix (ECM) is an essential and crucial process for physiological bone formation and pathological calcification. The abnormal function of ECM mineralization contributes to the worldwide risk of developing mineralization-related diseases; for instance, vascular calcification is attributed to the hyperfunction of ECM mineralization, while osteoporosis is due to hypofunction. AnnexinA6 (AnxA6), a Ca2+-dependent phospholipid-binding protein, has been extensively reported as an essential target in mineralization-related diseases such as osteoporosis, osteoarthritis, atherosclerosis, osteosarcoma, and calcific aortic valve disease. To date, AnxA6, as the largest member of the Annexin family, has attracted much attention due to its significant contribution to matrix vesicles (MVs) production and release, MVs-ECM interaction, cytoplasmic Ca2+ influx, and maturation of hydroxyapatite, making it an essential target in ECM mineralization. In this review, we outlined the recent advancements in the role of AnxA6 in mineralization-related diseases and the potential mechanisms of AnxA6 under normal and mineralization-related pathological conditions. AnxA6 could promote ECM mineralization for bone regeneration in the manner described previously. Therefore, AnxA6 may be a potential osteogenic target for ECM mineralization.Copyright © 2023 Yang, Pei, Su, Duan and Liu.