The article discusses the critical role of chromosomal cohesion and separation in maintaining genomic stability and their dysregulation in aneuploidy and tumorigenesis. Cohesin, a protein complex, ensures that sister chromatids remain tightly paired until the metaphase-to-anaphase transition, when cohesin is cleaved by the enzyme Separase. This process is essential for accurate chromosome segregation and genomic fidelity. Dysregulation of these processes can lead to aneuploidy, characterized by an abnormal number of chromosomes, which is a common feature in various cancers. Overexpression of Separase, an oncogene, is associated with chromosomal missegregation and aneuploidy, contributing to tumor development. Mutations in cohesin subunits, such as STAG2, are prevalent in multiple cancers and can disrupt genome organization and transcription, leading to cancer progression. The article highlights the potential of targeting Separase as a therapeutic approach to combat aneuploidy and cancer, offering a promising avenue for innovative cancer therapies.The article discusses the critical role of chromosomal cohesion and separation in maintaining genomic stability and their dysregulation in aneuploidy and tumorigenesis. Cohesin, a protein complex, ensures that sister chromatids remain tightly paired until the metaphase-to-anaphase transition, when cohesin is cleaved by the enzyme Separase. This process is essential for accurate chromosome segregation and genomic fidelity. Dysregulation of these processes can lead to aneuploidy, characterized by an abnormal number of chromosomes, which is a common feature in various cancers. Overexpression of Separase, an oncogene, is associated with chromosomal missegregation and aneuploidy, contributing to tumor development. Mutations in cohesin subunits, such as STAG2, are prevalent in multiple cancers and can disrupt genome organization and transcription, leading to cancer progression. The article highlights the potential of targeting Separase as a therapeutic approach to combat aneuploidy and cancer, offering a promising avenue for innovative cancer therapies.