Receptor-interacting serine/threonine-protein kinase 1

RIPK1 (receptor-interacting serine/threonine-protein kinase 1) is a 671-amino-acid kinase that serves as a central regulator of TNF-mediated cell death and inflammation. It functions both as an active kinase and as a kinase-independent scaffold protein, controlling the balance between apoptosis, necroptosis, and inflammatory signaling by orchestrating assembly of death-inducing complexes and modulating NF-κB pathway activation (UniProt: Q13546).

RIPK1 is widely expressed and plays critical roles in developmental apoptosis inhibition and innate immune responses. Mutations in RIPK1 are associated with immunodeficiency disorders including immunodeficiency 57 with autoinflammation (IMD57, MIM 618108) and autoinflammation with episodic fever and lymphadenopathy (AIEFL, MIM 618852), both characterized by dysregulated inflammatory cytokine production and early-onset infections (UniProt: Q13546).

In Alzheimer's disease, RIPK1 is upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of +0.69 (Chaparral AD proteomics). This elevation may reflect heightened necroptotic and inflammatory signaling in AD pathology, though the specific contribution of RIPK1-mediated cell death to neurodegeneration requires further investigation.