SIK2, also known as serine/threonine-protein kinase SIK2, is a crucial regulator involved in multiple biological processes. It plays a significant role in energy metabolism, regulating pathways such as glycolysis, gluconeogenesis, lipid synthesis, and fatty acids β-oxidation (FAO) [1]. It is also associated with DNA repair, cell motility, autophagy, and the Wnt/β-catenin signaling pathway, highlighting its overall biological importance in normal physiological functions and disease conditions. Genetic models, like gene knockout (KO) or conditional knockout (CKO) mouse models, can be valuable for studying SIK2's functions.

In ovarian cancer, SIK2 enhances the Warburg effect by promoting glycolysis and inhibiting oxidative phosphorylation and gluconeogenesis. It also regulates intracellular lipid metabolism through promoting lipid synthesis and FAO, which ultimately induces cancer cell growth, proliferation, invasion, metastasis, and therapeutic resistance [1]. Inhibiting SIK2 can enhance the sensitivity of ovarian and triple-negative breast cancer cells to PARP inhibitors. SIK2 inhibitors decrease DNA double-strand break repair functions, PARP enzyme activity, and phosphorylation of class-IIa histone deacetylases, repressing the functions of genes in the DNA repair pathway [3]. In uveal melanoma, the loss of the LKB1-SIK2 module drives tumor cell proliferation, and LKB1 loss enhances proliferation through SIK2 inhibition [2].

In conclusion, SIK2 is a key regulator in multiple biological processes. Model-based research, especially KO/CKO mouse models, has revealed its role in various disease areas such as ovarian cancer, triple-negative breast cancer, and uveal melanoma. Understanding SIK2's functions provides potential therapeutic strategies for these diseases.