AEN (apoptosis enhancing nuclease) is a DEDDh exonuclease family member that functions as a p53-regulated mediator of apoptosis in response to DNA damage 1. As an exonuclease with activity against single- and double-stranded DNA and RNA, AEN cleaves DNA substrates and colocalizes with other apoptotic nucleases (CAD, AIF) in the nucleus following ionizing radiation, amplifying DNA damage signals to enhance apoptosis 1. AEN is induced by p53 following genotoxic stress and synergistically increases apoptotic cell death when expressed, with its apoptotic function dependent on intact exonuclease activity 1. Beyond its canonical role in radiation-induced apoptosis, AEN exhibits antiviral properties independent of its catalytic function, suppressing porcine epidemic diarrhea virus replication by activating type I interferon (IFN-α, IFN-β) and interferon-stimulated gene (ISG) expression 2. Clinically, AEN is relevant to metabolic dysfunction-associated steatohepatitis (MASLD), where it functions downstream of p53 in a persistent DNA damage response pathway that promotes hepatocyte apoptosis, contributing to disease pathogenesis even after dietary intervention 3. These findings identify AEN as a critical node linking p53-dependent DNA damage surveillance to both apoptotic and innate immune responses.