SIK2 is a serine/threonine kinase that regulates multiple metabolic and signaling pathways. It phosphorylates key substrates including IRS1, TORCs (CREB coactivators), and EP300, thereby modulating insulin signaling, CREB-dependent transcription, and histone acetylation activity. Through these mechanisms, SIK2 influences fatty acid oxidation, autophagy, glucose metabolism, and immune responses. In cancer contexts, SIK2 drives pathological processes across multiple tumor types. In ovarian cancer, SIK2 phosphorylates MYLK to promote cell motility and metastasis 1, and regulates glucose and lipid metabolism to enhance the Warburg effect and tumor growth 2. In clear cell renal cell carcinoma, the FTO-autophagy-SIK2 axis promotes tumorigenesis by modulating SIK2 mRNA stability 3. In uveal melanoma, loss of the LKB1-SIK2 module drives proliferation through SLC8A1 upregulation and increased reactive oxygen species 4. Conversely, in Alzheimer's disease models, reduced SIK2 levels correlate with cognitive decline, and SIK2 restoration enhances autophagosome-lysosome fusion via GABARAPL2 phosphorylation, reducing amyloid-β pathology 5. SIK2 inhibitors represent an emerging therapeutic strategy. The dual SIK2/SIK3 inhibitor GLPG3970 modulates pro-inflammatory cytokine TNFα and immunoregulatory IL-10 in inflammatory disease models 6. In ovarian cancer, the novel SIK2 inhibitor SIC-19 shows synthetic lethality with PARP inhibitors by impairing RAD50-mediated DNA homologous recombination repair 7.