细胞死亡和炎症是先天免疫应对感染和组织功能障碍的两个密切相关的方面。最近我们对细胞死亡产生的复杂信号的认识进一步揭示了细胞死亡不仅仅是一个终点，更有助于在垂死细胞和组织微环境中的细胞，特别是免疫细胞之间交流信息，提醒并招募它们到干扰部位。受体互作丝氨酸/苏氨酸蛋白激酶 1 (RIPK1) 正在作为一个关键的应激哨兵浮出水面。它作为一个分子开关，通过调控细胞存活、炎症反应和免疫原性细胞死亡信号转导来维持严密的调节。它的严格调控涉及多层次的蛋白翻译后修饰。在本综述中，我们讨论了调节RIPK1以在健康细胞中维持稳态和细胞存活，同时在具体情境中诱导细胞死亡的分子机制。我们探讨了RIPK1突变或异常调控与炎症、自身免疫性疾病和癌症的关联。此外，我们也讨论了RIPK1的催化和非催化作用的已知情况，并对目前在临床中针对RIPK1的治疗策略的成功与不足进行了分析。© 2023. Springer Nature Limited.

Cell death and inflammation are closely linked arms of the innate immune response to combat infection and tissue malfunction. Recent advancements in our understanding of the intricate signals originating from dying cells have revealed that cell death serves as more than just an end point. It facilitates the exchange of information between the dying cell and cells of the tissue microenvironment, particularly immune cells, alerting and recruiting them to the site of disturbance. Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is emerging as a critical stress sentinel that functions as a molecular switch, governing cellular survival, inflammatory responses and immunogenic cell death signalling. Its tight regulation involves multiple layers of post-translational modifications. In this Review, we discuss the molecular mechanisms that regulate RIPK1 to maintain homeostasis and cellular survival in healthy cells, yet drive cell death in a context-dependent manner. We address how RIPK1 mutations or aberrant regulation is associated with inflammatory and autoimmune disorders and cancer. Moreover, we tease apart what is known about catalytic and non-catalytic roles of RIPK1 and discuss the successes and pitfalls of current strategies that aim to target RIPK1 in the clinic.© 2023. Springer Nature Limited.