NUAK2, a member of the AMP-activated protein kinase (AMPK) family, plays diverse roles in cellular processes. It is involved in pathways such as TGF-β signaling, where it fine-tunes the output of this crucial signaling cascade that regulates various cellular functions from proliferation and apoptosis to differentiation and migration [1].

In IBD, conditional knockout of Gpr65 in CD4+ T cells was studied. Gpr65 promotes Th1 and Th17 cell differentiation and gut inflammation by downregulating NUAK2. Gpr65 deficiency promoted NUAK2 expression via the cAMP-PKA-C-Raf-ERK1/2-LKB1-mediated signalling pathway, and silencing of Nuak2 facilitated Th1 and Th17 cell differentiation, suggesting its role in modulating CD4+ T cell immune responses in IBD [2].

In pancreatic cancer, inhibiting NUAK2 impeded cell proliferation, migration, invasion, and triggered apoptosis. NF-κB transcriptionally regulated NUAK2, and NUAK2 knockdown reduced p-SMAD2/3 and SMAD2/3 levels, affecting nuclear translocation of SMAD4. NUAK2 knockdown also heightened the sensitivity of pancreatic cancer cells to gemcitabine [3].

In peripheral nerve injury, NUAK2 was upregulated following distal sciatic nerve crush. NUAK2-deficient Schwann cells showed reduced expression of Yes-associated protein (YAP), and NUAK2 was speculated to be involved in Schwann cell proliferation and migration via YAP-driven processes [4].

In conclusion, NUAK2 is involved in multiple biological processes and diseases. Its study in gene knockout or conditional knockout models, such as in IBD, pancreatic cancer, and peripheral nerve injury, has revealed its importance in immune response regulation, cancer progression, and nerve regeneration, respectively. These findings provide insights into potential therapeutic strategies targeting NUAK2 in related diseases.