Eif2ak2, also known as protein kinase R (PKR), encodes a kinase that phosphorylates eukaryotic translation initiation factor 2 alpha (eIF2α), orchestrating the cellular stress response [4]. It is involved in multiple pathways such as endoplasmic reticulum stress response and is associated with various biological processes like immune response and inflammation [3]. Genetic models, like gene knockout mouse models, can be valuable for studying its functions.

In Eif2ak2 gene knockdown mice, the inhibitory effect of berberine on the secretion of inflammatory cytokines (IL-1β, IL-6, IL-18 and TNF-α) was attenuated, highlighting an Eif2ak2-dependent anti-inflammatory efficacy [1]. In septic AKI models, Eif2ak2 could directly target absent in melanoma 2 (AIM2), positively regulating its expression and promoting PANoptosis, a type of inflammatory programmed cell death [2]. Pharmacological and genetic inhibition of Eif2ak2 attenuated NLRP3 and AIM2 inflammasomes activation in macrophages, suppressing the release of cytokines like IL-1β and IL-18 in sepsis-related studies [5].

In conclusion, Eif2ak2 plays a crucial role in the cellular stress response, inflammation, and sepsis-associated cell death processes. Gene knockdown mouse models have been instrumental in revealing its role in anti-inflammatory effects and sepsis-induced acute kidney injury, providing insights into the underlying mechanisms of these disease-related processes [1,2,5].