IKKε (IκB kinase epsilon), also known as IKBKE, is a serine/threonine protein kinase that plays crucial roles in the [NF-κB](/entities/nf-kb) signaling pathway, innate immune response, and cellular stress responses. It is highly expressed in immune cells and [neurons](/entities/neurons), where it regulates inflammation, cell survival, and metabolic processes. IKKε has been implicated in the pathogenesis of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS)[@kravchenko2003].
Overview
IKKε is a non-canonical IκB kinase that shares structural and functional similarities with IKKα and IKKβ. Unlike the canonical IKK complex, IKKε is induced by cytokines and viral infection and preferentially phosphorylates IκB proteins to activate NF-κB signaling. IKKε also has diverse cellular functions beyond NF-κB, including regulation of insulin signaling, adipogenesis, and mitochondrial dynamics[@harper2003].
Structure
IKKε is a serine/threonine protein kinase with the following structural features:
Domain Architecture
Kinase domain (KD): Catalytic domain at the N-terminus with typical kinase fold
[Kravchenko VV, Mathison JC, Schwamborn K, et al, IKKi/IKKε plays a key role in integrating signals induced by pro-inflammatory stimuli (2003)](https://pubmed.ncbi.nlm.nih.gov/12746428/)
[Harper CV, Barr AR, Cantrell L, et al, The kinase IKKi/IKKε is a novel therapeutic target for inflammatory diseases (2003)](https://pubmed.ncbi.nlm.nih.gov/14506580/)
[Chen W, Li X, Huang H, et al, The role of IKKε in neurodegenerative diseases (2021)](https://pubmed.ncbi.nlm.nih.gov/34620159/)
[Gulen MF, Bulek K, Xiao H, et al, Inactivation of the kinase IKKε promotes the accumulation of proinflammatory macrophages and mice (2017)](https://pubmed.ncbi.nlm.nih.gov/28737749/)
[Chuang YF, Knight JM, David M, et al, IKKε deficiency reduces inflammation and improves survival in a model of bacterial pneumonia (2015)](https://pubmed.ncbi.nlm.nih.gov/25440771/)
[Zhang Q, Zong Q, Liao Y, et al, IKKε activation and function in neurons (2017)](https://pubmed.ncbi.nlm.nih.gov/29141660/)