RIPK1

RIPK1 stands for "Receptor-interacting serine/threonine protein kinase 1." RIPK1 is a serine/threonine protein kinase and a key signaling protein involved in inflammatory responses and regulated cell death.

RIPK1 has two functionally distinct roles: As a scaffold protein, RIPK1 supports, among other things, survival signals from the TNF receptor; when its kinase function is activated, it can contribute to the initiation of apoptosis or, via RIPK3 and MLKL, necroptosis. In the cytoplasmic ripoptosome , RIPK1 acts in conjunction with FADD and caspase-8.

Genetics and clinical significance: The RIPK1 gene, located on chromosome 6, encodes the protein of the same name, RIPK1. Biallelic loss-of-function variants can cause RIPK1 deficiency, leading to immunodeficiency and inflammatory diseases. Certain heterozygous variants, on the other hand, prevent the cleavage of RIPK1 by caspase-8 and lead to the autoinflammatory CRIA syndrome, which is characterized, among other things, by recurrent fever and lymphadenopathy.

As a key mediator of cell death and inflammatory processes, RIPK1 is a target for the development of highly selective small-molecule inhibitors. Potential applications of RIPK1 inhibitors are emerging for the treatment of monogenic and polygenic autoimmune, inflammatory, neurodegenerative, ischemic, and acute diseases, such as sepsis (Mifflin L et al. 2020).

1. Chen Z et al. (2025) RIPK1 detects a shortage of S-adenosylmethionine to trigger cell death and inflammation. Cell Metab 37:1732-1749.e9.
2. Dannappel M et al. (2014) RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature 513(7516):90–94.
3. Mifflin L et al. (2020) Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target. Nat Rev Drug Discov 19:553–571.