Proprotein convertase subtilisin/kexin type 9 (PCSK9) has a crucial role in lipid metabolism, particularly due to its function in low‐density lipoprotein receptor degradation. Gain‐of‐function genetic mutations of PCSK9 result in autosomal dominant familial hypercholesterolemia, characterized by high levels of low‐density lipoprotein cholesterol (LDL‐C) and clinical signs of early atherosclerosis. In recent years, PCSK9 has become an important therapeutic target for cholesterol‐lowering therapy. Particularly, its inhibition with monoclonal antibodies has shown excellent efficacy in decreasing LDL‐C and reducing cardiovascular events. However, PCSK9, first identified in the brain, seems to be a ubiquitous protein with different tissue‐specific functions also independent of cholesterol metabolism. Accordingly, it appears to be involved in the immune response, haemostasis, glucose metabolism, neuronal survival, and several other biological functions. This review provides a comprehensive overview of the genetics, biochemical structure, expression, and function of PCSK9 and discusses the potential implications of its long‐term pharmacological inhibition.

中文翻译：

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胆固醇代谢之外：前蛋白转化酶枯草杆菌蛋白酶/ kexin 9型（PCSK9）的多效性作用。遗传，突变，表达和长期抑制的观点。

前蛋白转化酶枯草杆菌蛋白酶/ kexin 9型（PCSK9）在脂质代谢中起着至关重要的作用，特别是由于其在低密度脂蛋白受体降解中的作用。PCSK9的功能获得性遗传突变导致常染色体显性家族性高胆固醇血症，其特征在于高水平的低密度脂蛋白胆固醇（LDL-C）和早期动脉粥样硬化的临床体征。近年来，PCSK9已成为降低胆固醇治疗的重要治疗靶标。特别是，它对单克隆抗体的抑制作用在降低LDL-C和减少心血管事件方面显示出卓越的功效。但是，首先在大脑中鉴定出的PCSK9似乎是一种遍在蛋白，具有不同的组织特异性功能，并且与胆固醇代谢无关。因此，它似乎参与了免疫反应，止血，葡萄糖代谢，神经元存活和其他几种生物学功能。这篇评论全面概述了遗传学，生化结构，表达，