在ERAD过程中，待降解的底物（分三种：ERAD-L (lumen)、ERAD-M (membrane)和ERAD-C (cytosol)）通过E3连接酶标记上泛素，之后，通过特定的运输机制运回到细胞质中，然后，被细胞质26S蛋白酶体所降解。

2025年2月4日 · Two key pathways for eliminating misfolded proteins and aggregates in the ER are ER-associated degradation (ERAD) and ER-phagy, respectively. While both pathways have been well characterized biochemically, our understanding of their physiological relevance and significance remains limited.

Endoplasmic-reticulum-associated protein degradation (ERAD) designates a cellular pathway which targets misfolded proteins of the endoplasmic reticulum for ubiquitination and subsequent degradation by a protein-degrading complex, called the proteasome. The process of ERAD can be divided into three steps:

未折叠蛋白反应（UPR）通过包括内质网相关性降解（ER-associated degradation, ERAD）在内的多种机制维持内质网稳态。ERAD识别末端错误折叠或未组装的蛋白，并让它们跨过内质网膜逆向转位到细胞质中，在那里它们被蛋白酶体降解。

2008年11月12日 · Endoplasmic reticulum (ER)-associated degradation (ERAD) is a secretory protein quality control process that results in the removal of aberrant proteins...

2023年8月1日 · ERAD serves two principal physiological roles: first, protection against the accumulation of defective, slow-folding or unfolding proteins that might otherwise be toxic and impede secretory...

2022年2月16日 · ERAD regulates ER functions primarily via its role in the degradation of membrane proteins. However, the mechanism of ERAD is best understood for luminal (ERAD‐L) substrates, which are targeted to the Hrd1 complex in both yeast and mammals.

Endoplasmic reticulum (ER)-associated degradation (ERAD) is a mechanism against ER stress, wherein unfolded/misfolded proteins accumulated in the ER are transported to the cytosol for degradation by the ubiquitin-proteasome system.

2020年4月24日，哈佛医学院 Tom Rapoport 实验室与合作者（第一作者为 吴旭冬 博士）在 Science 杂志上以研究长文 (Research Article) 的形式发表了题为 Structural basis of ER-associated protein degradation mediated by the Hrd1 ubiquitin ligase complex 的文章 。 该论文使用冷冻电子显微镜（cryo-EM）解析了整个Hrd1复合体的三维结构。 通过这些结构、体内交联和活性分析实验，以及大量的分子动力学模拟，作者揭示了Hrd1复合物如何招募蛋白质底物，并协 …

Misfolded proteins of the endoplasmic reticulum (ER) are discarded by a conserved process, called ER-associated protein degradation (ERAD). ERAD substrates are retro-translocated into the cytosol, polyubiquitinated, extracted from the ER …