Mark3, also known as Microtubule affinity-regulating kinase 3, is a member of the MARK family. It contains an N-terminal serine/threonine kinase domain, ubiquitin-associated domain, and C-terminal kinase-associated domain, performing multiple regulatory functions like post-translational modification and protein-protein interactions. It regulates essential pathways such as the cell cycle, ciliated cell differentiation, and osteoclast differentiation, and thus is of great biological importance [1].

In mice, global or osteoblast-specific deletion of Mark3 leads to increased bone mass at maturity. Mark3-deficient osteoblasts show greater matrix mineralization, reduced Jag1/Hes1 expression, and diminished downstream JNK signaling. Overexpression of Jag1 in these osteoblasts normalizes mineralization capacity and bone mass, revealing a mechanism by which Mark3 influences bone mass [4]. In high-grade serous ovarian carcinoma (HGSOC), downregulation of MARK3 significantly correlates with poor prognosis. MARK3 overexpression suppresses cell proliferation and angiogenesis of ovarian cancer cells, and the LKB1-MARK3 axis, activated by metabolic stress, leads to G2/M phase arrest [3]. In endometrial cancer cell lines, MARK3 overexpression reduces colony formation and cell viability, suggesting its role in regulating cell survival pathways [2].

In conclusion, Mark3 is crucial in regulating multiple biological processes. Its role in diseases like osteoporosis and certain cancers has been revealed through mouse models. These models have provided insights into the mechanisms by which Mark3 affects bone mass and tumor-related processes, offering potential directions for disease treatment and prevention.