Receptor interacting protein kinase 1 as a potential therapeutic target in inflammatory bowel disease: biological...

Inflammatory bowel disease (IBD) remains a major cause of morbidity, with many patients failing to achieve sustained remission and mucosal healing. Receptor-interacting protein kinase 1 (RIPK1) is a potential therapeutic target that links tumor necrosis factor receptor signaling to inflammation, apoptosis, and necroptosis, processes relevant to epithelial injury and barrier dysfunction in IBD.

This narrative review summarizes the biological rationale and translational and clinical evidence for targeting RIPK1 in IBD. MEDLINE was searched from database inception to March 2026 to identify relevant articles. Preclinical studies across cell systems, human tissue, and murine colitis models, suggest that RIPK1 kinase activity contributes to inflammatory signaling, epithelial injury, and necroptosis, while selective inhibition attenuates these processes and ameliorates experimental colitis. However, RIPK1 also has kinase-independent scaffolding functions important for epithelial homeostasis, highlighting the complexity of therapeutic targeting. GSK2982772 did not demonstrate convincing efficacy, whereas clinical efficacy data for newer RIPK1 inhibitors, including ABBV-668 and eclitasertib, have not yet been reported.

RIPK1 remains a compelling but clinically unvalidated target in IBD. Future progress will depend on improved patient selection, confirmation of mucosal target engagement, and better recognition of patients in which RIPK1 signaling is a key driver.