Receptor Interacting Protein Kinase 1 (RIPK1) is a key regulator of inflammation. To warrant cell survival and appropriate immune responses, RIPK1 is post-translationally regulated by ubiquitylations, phosphorylations and caspase-8-mediated cleavage. Dysregulations of these post-translational modifications switch on the pro-death function of RIPK1 and can cause inflammatory diseases in humans. Conversely, activation of RIPK1 cytotoxicity can be advantageous for cancer treatment. Small molecules targeting RIPK1 are under development for the treatment of cancer, inflammatory and neurogenerative disorders. We will discuss the molecular mechanisms controlling the functions of RIPK1, its pathologic role in humans and the therapeutic opportunities in targeting RIPK1, specifically in the context of inflammatory diseases and cancers.

受体相互作用蛋白激酶 1 (RIPK1) 是炎症的关键调节剂。为了保证细胞存活和适当的免疫反应，RIPK1 受到泛素化、磷酸化和 caspase-8 介导的切割的翻译后调节。这些翻译后修饰的失调会开启 RIPK1 的促死亡功能，并可能导致人类炎症性疾病。相反，激活 RIPK1 细胞毒性可能有利于癌症治疗。针对 RIPK1 的小分子正在开发中，用于治疗癌症、炎症和神经系统疾病。我们将讨论控制 RIPK1 功能的分子机制、其在人类中的病理作用以及靶向 RIPK1 的治疗机会，特别是在炎症性疾病和癌症的背景下。