Keap1, also known as Kelch-like ECH-associated protein 1, is a crucial component in the Nrf2-Keap1 signaling pathway [1-10]. It acts as an endogenous inhibitor of Nrf2, a transcription factor. Under normal conditions, Keap1 binds to Nrf2, targeting it for proteasomal degradation. However, in the presence of oxidative or electrophilic stress, this interaction is disrupted, allowing Nrf2 to translocate to the nucleus and activate the transcription of cytoprotective genes [1-5, 7-9]. This system is a fundamental intracellular defense mechanism against oxidative stress, conserved evolutionarily, and is involved in maintaining redox homeostasis [1,2].

In breast cancer, Keap1 has been shown to be a positive prognostic factor. It regulates cell proliferation, apoptosis, and cell cycle transition, and controls mitochondrial biogenesis by promoting the degradation of HSPA9 through ubiquitination [3]. In sepsis, a small-molecule inhibitor of the Keap1-Nrf2 interaction, IR-61, preferentially accumulates in macrophages at infection sites. By directly inhibiting the Keap1-Nrf2 interaction, it activates Nrf2, enhancing the antibacterial function of macrophages, bacterial clearance, and improving sepsis outcomes in mouse models [4].

In conclusion, Keap1 plays a vital role in the Nrf2-Keap1 signaling pathway, which is essential for protecting cells from oxidative stress. Studies using models such as mouse models in breast cancer and sepsis have revealed its significance in disease-related biological processes. These findings contribute to understanding the role of Keap1 in specific disease areas, potentially providing new therapeutic targets for treatment [3,4].