EIF2AK2 (protein kinase R/PKR) is an interferon-induced serine/threonine kinase that serves as a critical sentinel in innate antiviral immunity 1. Upon detection of double-stranded RNA (dsRNA) from viral or endogenous sources, EIF2AK2 phosphorylates eukaryotic translation initiation factor 2 alpha (eIF2α), triggering the integrated stress response (ISR) 2. This phosphorylation event halts global protein synthesis while selectively promoting translation of stress-response transcripts including ATF4, effectively suppressing both viral and cellular protein production 2. EIF2AK2 exerts broad antiviral activity against diverse DNA and RNA viruses including hepatitis C, measles virus, and herpes simplex virus. Beyond canonical viral defense, EIF2AK2 regulates inflammasome activation, apoptosis, and signal transduction through phosphorylation of multiple substrates and interaction with signaling proteins 34. The kinase can activate inflammatory pathways (NF-κB, p38 MAPK) while simultaneously modulating autophagy through interactions with STAT3 5. Disease-relevant mutations in EIF2AK2 cause dystonia 33 and leukoencephalopathy with developmental delay, implicating endoplasmic reticulum stress response dysfunction in neurological pathology 6. Additionally, EIF2AK2-mediated AIM2 inflammasome activation contributes to septic acute kidney injury through PANoptosis, a combined form of programmed cell death 4.