Proteostasis refers to all the processes that maintain the correct expression level, location, folding and turnover of proteins, essential to organismal survival. Both inside cells and in body fluids, molecular chaperones play key roles in maintaining proteostasis. In this article, we focus on clusterin, the first-recognized extracellular mammalian chaperone, and its role in diseases of the eye. Clusterin binds to and inhibits the aggregation of proteins that are misfolded due to mutations or stresses, clears these aggregating proteins from extracellular spaces, and facilitates their degradation. Clusterin exhibits three main homeostatic activities: proteostasis, cytoprotection, and anti-inflammation. The so-called "protein misfolding diseases” are caused by aggregation of misfolded proteins that accumulate pathologically as deposits in tissues; we discuss several such diseases that occur in the eye. Clusterin is typically found in these deposits, which is interpreted to mean that its capacity as a molecular chaperone to maintain proteostasis is overwhelmed in the disease state. Nevertheless, the role of clusterin in diseases involving such deposits needs to be better defined before therapeutic approaches can be entertained. A more straightforward case can be made for therapeutic use of clusterin based on its proteostatic role as a proteinase inhibitor, as well as its cytoprotective and anti-inflammatory properties. It is likely that clusterin works together in this way with other extracellular chaperones to protect the eye from disease, and we discuss several examples. We end this article by predicting future steps that may lead to development of clusterin as a biological drug.

蛋白质稳态是指维持蛋白质正确表达水平、位置、折叠和周转的所有过程，这对生物体生存至关重要。在细胞内部和体液中，分子伴侣在维持蛋白质稳态方面发挥着关键作用。在本文中，我们重点关注簇蛋白（第一个被认可的细胞外哺乳动物伴侣）及其在眼部疾病中的作用。凝聚蛋白结合并抑制由于突变或应激而错误折叠的蛋白质的聚集，从细胞外空间清除这些聚集的蛋白质，并促进其降解。Clusterin 表现出三种主要的稳态活性：蛋白质稳态、细胞保护和抗炎。我们讨论了几个例子。我们通过预测未来可能导致凝聚素开发为生物药物的步骤来结束本文。