WEE1 is a crucial cell cycle checkpoint kinase that acts as a negative regulator of mitotic entry by controlling the G2/M transition 1. The primary function involves phosphorylating and inactivating cyclin B1-complexed CDK1 on tyrosine-15, preventing premature mitosis and maintaining genomic stability 2. WEE1 activity peaks during S and G2 phases and decreases at M phase through hyperphosphorylation and protein degradation. Mechanistically, WEE1 functions within the ATR-CHK1-WEE1 pathway that controls S and G2/M checkpoints, particularly important when the G1 checkpoint is compromised in cancer 1. In cancer contexts, WEE1 exhibits dual roles as both tumor suppressor in normal cells and pseudo-oncogene in malignant cells 3. Disease relevance is significant in cancers with TP53 mutations, where WEE1 inhibition enhances apoptosis through mitotic catastrophe by promoting uncontrolled G2/M transition and reducing DNA damage response proteins like CHK2 and Rad51 4. Clinical significance includes the development of WEE1 inhibitors as cancer therapeutics, showing particular promise in TP53-mutated tumors and when combined with chemotherapy or other targeted agents, though optimal biomarkers and treatment combinations are still being defined 5 6.