Many human diseases are associated with mutations causing protein misfolding and aggregation in the endoplasmic reticulum (ER). ER-associated degradation (ERAD) is a principal quality-control mechanism responsible for targeting misfolded ER proteins for cytosolic degradation. However, despite years of effort, the physiological role of ERAD in vivo remains largely unknown. Several recent studies have reported intriguing phenotypes of mice deficient for ERAD function in specific cell types. These studies highlight that mammalian ERAD has been designed to perform a wide-range of cell-type-specific functions in vivo in a substrate-dependent manner.

中文翻译：

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内质网相关降解的生理作用的新见解

许多人类疾病与引起蛋白质错误折叠和内质网（ER）聚集的突变有关。ER相关降解（ERAD）是主要的质量控制机制，负责靶向错误折叠的ER蛋白进行胞质降解。然而，尽管付出了多年的努力，但ERAD在体内的生理作用仍然未知。最近的一些研究报道了在特定细胞类型中缺乏ERAD功能的小鼠的有趣表型。这些研究突出表明，哺乳动物ERAD已被设计为以底物依赖性方式在体内执行多种细胞类型特异性功能。