The receptor-interacting protein kinases (RIPKs) are key regulators of inflammatory signalling and cell death pathways triggered by innate immune receptors, and RIPKs have emerged as promising therapeutic targets for treatment of immune-related disorders. RIPK2 mediates signalling responses initiated by the bacterial-sensing pattern recognition receptors nucleotide-binding oligomerization domain-containing proteins 1 and 2 (NOD1/2), which play a key role in regulation of intestinal immunity and inflammation. Modification of RIPK2 by non-degradative ubiquitin chains generated by the E3 ubiquitin ligase XIAP and other ligases govern NOD1/2 signalling. Recent advances suggest that the interaction between RIPK2 and XIAP is a druggable protein-protein interaction to modulate NOD1/2-dependent immune responses. Here, we discuss the mechanistic function of RIPK2 in immune signalling, its clinical relevance, and the on-going efforts to target RIPK2 in inflammatory bowel disease and beyond.

受体相互作用蛋白激酶 (RIPKs) 是先天免疫受体触发的炎症信号和细胞死亡途径的关键调节剂，RIPKs 已成为治疗免疫相关疾病的有希望的治疗靶点。RIPK2 介导由细菌感应模式识别受体核苷酸结合寡聚化结构域蛋白 1 和 2 (NOD1/2) 启动的信号反应，它们在调节肠道免疫和炎症中起关键作用。由 E3 泛素连接酶 XIAP 和其他连接酶产生的非降解泛素链对 RIPK2 的修饰控制 NOD1/2 信号传导。最近的进展表明 RIPK2 和 XIAP 之间的相互作用是一种可药物的蛋白质-蛋白质相互作用，可调节 NOD1/2 依赖性免疫反应。这里，