SIK2 (salt-inducible kinase 2) is a serine/threonine-protein kinase that regulates multiple metabolic and cellular processes. Primary functions include modulating fatty acid oxidation, autophagy, immune response, and glucose metabolism 12. SIK2 phosphorylates IRS1 in insulin-stimulated adipocytes, potentially modulating insulin signal transduction, and inhibits CREB activity by phosphorylating TORCs 3. The kinase also phosphorylates EP300 to inhibit its histone acetyltransferase activity, thereby regulating transcription factors like PPARA and MLXIPL 42. Mechanistically, SIK2 phosphorylates GABARAPL2 at Ser72 to facilitate autophagosome-lysosome fusion, critical for autophagic flux 5. Disease relevance is significant across multiple cancers: SIK2 mutations occur in lung adenocarcinoma 6; the LKB1-SIK2 module restrains uveal melanoma tumorigenesis, with SIK2 loss promoting proliferation 7; in renal cell carcinoma, FTO-mediated autophagy regulates SIK2 mRNA stability to promote progression 8; and in ovarian cancer, SIK2 enhances the Warburg effect and regulates lipid metabolism 9. Clinically, SIK2 inhibition shows promise: SIC-19, a novel SIK2 inhibitor, exhibits synthetic lethality with PARP inhibitors by impairing DNA homologous recombination repair 10, while SIK2 restoration mitigates Alzheimer's disease pathology 5.