NUAK2 is a stress-activated kinase belonging to the AMP-activated protein kinase (AMPK)-related kinase family 1. It regulates cellular responses to metabolic stress, particularly glucose starvation, and modulates actin cytoskeleton dynamics by promoting F-actin to G-actin conversion, thereby facilitating cell motility and detachment [UniProt]. NUAK2 exerts its effects primarily through phosphorylation of LATS1 and LATS2, key components of the Hippo signaling pathway, which regulates YAP1 nuclear localization critical for neural tube closure during embryonic development [UniProt]. The kinase is activated by CD95 and TNF signaling via NF-κB and protects cells from CD95-mediated apoptosis while promoting tumor cell invasiveness [UniProt]. NUAK2 has emerged as a significant oncogenic driver across multiple cancer types. In melanoma, high NUAK2 expression correlates with increased tumor thickness and is associated with poor relapse-free survival in acral melanoma patients (hazard ratio=3.88) 2. Similarly, NUAK2 is elevated in prostate cancer and metastatic castration-resistant disease, where it promotes cell proliferation, invasion, and YAP-dependent oncogenic transcription 3. In low-grade glioma, NUAK2 drives tumor progression and immune suppression through ferroptosis dysregulation 4. Additionally, NUAK2 functions as a host-dependency factor for SARS-CoV-2 and related coronaviruses, facilitating viral entry by maintaining ACE2 cell surface levels through actin cytoskeleton modulation 5. NUAK2 kinase inhibitors represent promising therapeutic agents for cancer and viral infections 6.