Microtubule-associated serine/threonine kinase-like (MASTL) is the functional mammalian ortholog of Greatwall kinase (Gwl), which was originally discovered in Drosophila. The human MASTL (Microtubule-associated serine/threonine kinase-like) gene encodes an essential protein in the cell cycle. MASTL is a key factor preventing early dephosphorylation of M-phase targets of Cdk1/CycB. MASTL kinase is a master regulator of mitosis, essential for ensuring that mitotic substrate phosphorylation is correctly maintained. MASTL controls the final G2/M checkpoint and prevents premature entry of cells into mitosis. Loss of MASTL causes chromosome segregation errors, mitotic collapse, and failure of cytokinesis. However, in cancer MASTL is most commonly amplified and overexpressed. This correlates with increased chromosome instability in breast cancer and poor patient survival in breast, ovarian, and lung cancer. MASTL kinase promotes mitotic progression and cell cycle reentry after DNA damage.