Tumor cells frequently hijack RIPK1’s scaffolding function to resist cell death and avoid immune detection. Mannion et al. describe the development of a RIPK1-selective PROTAC degrader that boosts the...

AbstractIntroduction. CASPASE8 promotes both cell death and survival by acting as a trigger of apoptosis and a repressor of necroptosis. In T cells, the fu

ZBP1 is known to initiate RIPK3-mediated necroptosis in murine models of viral infection, but how this pathway is regulated in human cells is unclear. This study shows that, unlike in the mouse, RIPK1...

Pharmacological degradation of receptor-interacting protein kinase 1 (RIPK1) offers a compelling therapeutic strategy to overcome its scaffolding role in tumor resistance and enhance the efficacy of i...

ZBP1 is known to initiate RIPK3-mediated necroptosis in murine models of viral infection, but how this pathway is regulated in human cells is unclear. This study shows that, unlike in the mouse, RIPK1...

Microglia-mediated neuroinflammation drives Alzheimer's disease (AD) pathogenesis, yet the underlying mechanism is poorly understood. Song et al. demonstrate that toxic amyloid-β induces oxidation and...

ZBP1 is known to initiate RIPK3-mediated necroptosis in murine models of viral infection, but how this pathway is regulated in human cells is unclear. This study shows that, unlike in the mouse, RIPK1...

How cells sense nutrients to maintain homeostasis and prevent cell death is a fundamental question. Chen et al. reveal that cells use RIPK1 to sense levels of the nutrient methionine and its metabolit...

We report an efficient, stereocontrolled, and chromatography-free first-generation manufacturing process for GDC-8264 (1), a RIPK1 inhibitor. Key steps include a diastereoselective reductive amination...

The function of the Alzheimer’s disease (AD) risk gene INPP5D in microglia remains unclear. Xie et al. identify INPP5D as a direct regulator of RIPK1 kinase, known to be implicated in mediating neuroinflammation. They show that INPP5D deficiency in aging activates RIPK1-dependent diverse innate immune signaling, promoting TDP-43 pathology and neuronal loss associated with AD and motoneuron degeneration, such as amyotrophic lateral sclerosis (ALS).

Chen et al. show that reduced brain glucose metabolism and pathological Tau cooperate to induce neuronal death through necroptosis. By identifying a p-Tau-RIPK1 signaling hub and its regulation by A20...

Injection of YopJ by Yersinia pseudotuberculosis triggers RIPK1-dependent caspase-8 and GSDMD activation in murine macrophages; however, how macrophages defend against Yersinia when caspase-8 or YopJ ...

imageimageAblation of RIPK1 in αβT cells results in spontaneous proximal small intestinal pathology, characterized by microbiome-mediated epithelial hyperproliferation and TNF-driven villus atrophy, u...

It has been shown that targeting receptor-interacting protein kinase 1 (RIPK1) can improve response to immune checkpoint inhibitors. Here, using PROTAC technology, the authors report the design and ch...

A Breakthrough in COVID-19 Therapeutics: Synergistic Targeting of SARS-CoV-2 PLpro and Host RIPK1 Yields Promising Results in Preclinical Models The global battle against COVID-19 continues to demand

TBK1 and IKKe prevent premature cell death by limiting the activity of multiple death pathways in myeloid cells.