Receptor-Interacting Protein Kinase 1 (RIPK1): A Potential Therapeutic Target in Ischemic Stroke.

Receptor-interacting protein kinase 1 (RIPK1) is a pivotal molecule regulating cell death and inflammatory signaling pathways, with its activity tightly modulated by multiple post-translational modifications. While its involvement in various pathological processes is recognized, its precise regulatory roles and underlying mechanisms in ischemic stroke remain incompletely defined. Accumulating evidence indicates that RIPK1 modulates apoptotic and necroptotic cascades, neuroinflammation, and NF-κB pathway activation, thereby serving as a contributing factor that collaborates with other molecular pathways to influence stroke progression and outcome. In this review, we first summarize current insights into the molecular structure and biological functions of RIPK1, emphasizing the regulatory networks established by its post-translational modifications. We then dissect the multifaceted mechanisms by which RIPK1 participates in ischemic stroke pathology, including its roles in cell death, neuroinflammation, and blood-brain barrier integrity, as well as its potential as a diagnostic indicator for ischemic brain injury. Finally, we present a concise overview of the development status of RIPK1 inhibitors, which covers preclinical candidates and clinical trial-stage agents, aiming to inform future research endeavors and guide clinical translation for ischemic stroke treatment.