Receptor-interacting serine threonine kinase 1 (RIPK1) is a widely expressed kinase that is essential for limiting inflammation in both mice and humans. Mice lacking RIPK1 die at birth from multiorgan inflammation and aberrant cell death, whereas humans lacking RIPK1 are immunodeficient and develop very early-onset inflammatory bowel disease. In contrast to complete loss of RIPK1, inhibiting the kinase activity of RIPK1 genetically or pharmacologically prevents cell death and inflammation in several mouse disease models. Indeed, small molecule inhibitors of RIPK1 are in phase I clinical trials for amyotrophic lateral sclerosis, and phase II clinical trials for psoriasis, rheumatoid arthritis, and ulcerative colitis. This review focuses on which signaling pathways use RIPK1, how activation of RIPK1 is regulated, and when activation of RIPK1 appears to be an important driver of inflammation.

中文翻译：

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多任务激酶 RIPK1 调节细胞死亡和炎症。

受体相互作用的丝氨酸苏氨酸激酶 1 (RIPK1) 是一种广泛表达的激酶，对于限制小鼠和人类的炎症至关重要。缺乏 RIPK1 的小鼠在出生时死于多器官炎症和异常细胞死亡，而缺乏 RIPK1 的人类则存在免疫缺陷，并且会发展为非常早发的炎症性肠病。与完全丧失 RIPK1 相比，在几种小鼠疾病模型中，通过基因或药理学抑制 RIPK1 的激酶活性可防止细胞死亡和炎症。事实上，RIPK1 的小分子抑制剂正处于肌萎缩侧索硬化症的 I 期临床试验和银屑病、类风湿性关节炎和溃疡性结肠炎的 II 期临床试验中。本综述重点关注哪些信号通路使用 RIPK1，如何调节 RIPK1 的激活，