| Protein Name | Kelch-Like ECH-Associated Protein 1 |
|---|---|
| Gene | [KEAP1](/genes/keap1) |
| UniProt ID | [Q14145](https://www.uniprot.org/uniprot/Q14145) |
| Molecular Weight | 70 kDa |
| Subcellular Localization | Cytoplasm, Cytoskeleton |
| Protein Family | Kelch family |
| Gene Location | 19p13.2 |
KEAP1 (Kelch-Like ECH-Associated Protein 1) is a cysteine-rich adaptor protein that serves as the primary sensor of oxidative stress in cells[1][2]. It functions as the negative regulator of NRF2 (Nuclear Factor Erythroid 2-Related Factor 2), the master transcription factor coordinating cellular antioxidant responses. The KEAP1-NRF2 pathway is one of the most important cellular defense mechanisms against oxidative damage and has been heavily implicated in neurodegenerative diseases including Alzheimer's, Parkinson's, and Huntington's disease[3].
KEAP1 has a distinctive architecture with multiple functional domains:
KEAP1 contains over 25 reactive cysteine residues that sense electrophiles and oxidative stress[4].
KEAP1 functions as a molecular sensor:
KEAP1 acts as a substrate adaptor:
The pathway regulates:
KEAP1 dysregulation contributes to AD pathogenesis[5]:
The pathway is critical in PD:
KEAP1-NRF2 in HD:
KEAP1 is a major therapeutic target:
KEAP1: structure and function (2018). Cellular and Molecular Life Sciences. 2018. ↩︎
The KEAP1-NRF2 pathway in stress response (2020). Nature Reviews Molecular Cell Biology. 2020. ↩︎
KEAP1-NRF2 in neurodegeneration (2021). Journal of Neurochemistry. 2021. ↩︎
Cysteine sensing by KEAP1 (2019). Antioxidants & Redox Signaling. 2019. ↩︎
NRF2 activators for Alzheimer's disease (2022). Free Radical Biology and Medicine. 2022. ↩︎