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 such as post-translational modification and protein-protein interaction. Mark3 regulates essential pathways including the cell cycle, ciliated cell differentiation, and osteoclast differentiation, and is thus of great biological importance [1].

Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway, with reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts normalized mineralization capacity and bone mass, respectively, revealing a mechanism where Mark3 influences bone mass [3]. In high-grade serous ovarian carcinoma (HGSOC), the expression levels of Mark3 are downregulated, and its downregulation significantly correlates with poor prognosis. Mark3 overexpression suppresses cell proliferation and angiogenesis of ovarian cancer cells, and the LKB1-Mark3 axis can lead to G2/M phase arrest [2].

In conclusion, Mark3 plays crucial roles in regulating cell-related processes and in diseases like osteoporosis and ovarian cancer. Gene-knockout mouse models have been instrumental in uncovering its functions in bone mass regulation and cancer-related biological processes, enhancing our understanding of the underlying mechanisms and potentially guiding future therapeutic strategies.