Eif2ak2, also known as protein kinase R (PKR), is a key enzyme that phosphorylates eukaryotic translation initiation factor 2 alpha (eIF2α), orchestrating the cellular stress response. It is involved in multiple pathways such as endoplasmic reticulum stress response, and has been linked to various biological processes including inflammation, neurological function, and the immune response [1,2,4,5]. Gene knockout models can be valuable in studying Eif2ak2 to understand its role in these processes.

In Eif2ak2 gene knockdown mice, the inhibitory effect of berberine on the secretion of pro-inflammatory cytokines like IL-1β, IL-6, IL-18 and TNF-α was attenuated, highlighting its key role in berberine-mediated anti-inflammatory effects [1]. Variants in Eif2ak2 have been associated with a spectrum of neurological diseases, including childhood-onset generalized dystonia, fever-related neurological decompensation, movement disorders, and leukodystrophy [2]. In septic acute kidney injury, Eif2ak2 can directly target absent in melanoma 2 (AIM2), promoting AIM2-mediated PANoptosis [3].

In conclusion, Eif2ak2 is essential for regulating the cellular stress response and is involved in inflammation, neurological function, and immune-related processes. Studies using Eif2ak2-related gene knockout models have revealed its significant role in anti-inflammatory responses, neurological disease development, and septic acute kidney injury, providing insights into the underlying mechanisms of these diseases and potential therapeutic strategies.