CRELD2是囊泡蛋白家族囊泡蛋白质富含表皮生长因子样结构域（CRELD）蛋白质家族的成员，既是内质网（ER）驻留蛋白质，也是一种分泌因子。ER应激可以显著诱导CRELD2的表达和分泌。CRELD2在多种组织中广泛表达且表达水平不同，这表明它在不同组织中发挥着重要和多样化的作用。最近的研究表明，CRELD2与软骨/骨代谢平衡以及涉及ER应激的疾病，如慢性肝脏疾病、心血管疾病、肾脏疾病和癌症等有关。在本文中，我们首先总结ER应激，然后批判性地回顾CRELD2在各种人类疾病中的特性和功能的最新进展。此外，我们重点介绍了面临的挑战，并提出了未来探明CRELD2在人类健康和疾病中作用的方向。版权所有©2023 Tang, Liu, Li, Mo和He。

CRELD2, a member of the cysteine-rich epidermal growth factor-like domain (CRELD) protein family, is both an endoplasmic reticulum (ER)-resident protein and a secretory factor. The expression and secretion of CRELD2 are dramatically induced by ER stress. CRELD2 is ubiquitously expressed in multiple tissues at different levels, suggesting its crucial and diverse roles in different tissues. Recent studies suggest that CRELD2 is associated with cartilage/bone metabolism homeostasis and pathological conditions involving ER stress such as chronic liver diseases, cardiovascular diseases, kidney diseases, and cancer. Herein, we first summarize ER stress and then critically review recent advances in the knowledge of the characteristics and functions of CRELD2 in various human diseases. Furthermore, we highlight challenges and present future directions to elucidate the roles of CRELD2 in human health and disease.Copyright © 2023 Tang, Liu, Li, Mo and He.