The article discusses the versatility and transformative potential of Cas9, a single factor that can colocalize RNA, DNA, and protein. Cas9, derived from CRISPR-Cas systems, has revolutionized genome editing in diverse organisms. The authors detail the Cas9 targeting methodology, current and future engineering advances, and potential applications in basic science, cellular engineering, and therapeutics. They highlight the ability of Cas9 to bring together any fusion protein, RNA, or DNA sequence, enabling precise control over cellular organization, regulation, and behavior. The article also explores methods to enhance the efficacy, specificity, and versatility of Cas9-mediated genome editing, including multiplexed activities, improved targeting biases, and therapeutic applications. Despite challenges such as off-target effects and specificity, the authors envision Cas9 as a powerful tool for engineering living systems.The article discusses the versatility and transformative potential of Cas9, a single factor that can colocalize RNA, DNA, and protein. Cas9, derived from CRISPR-Cas systems, has revolutionized genome editing in diverse organisms. The authors detail the Cas9 targeting methodology, current and future engineering advances, and potential applications in basic science, cellular engineering, and therapeutics. They highlight the ability of Cas9 to bring together any fusion protein, RNA, or DNA sequence, enabling precise control over cellular organization, regulation, and behavior. The article also explores methods to enhance the efficacy, specificity, and versatility of Cas9-mediated genome editing, including multiplexed activities, improved targeting biases, and therapeutic applications. Despite challenges such as off-target effects and specificity, the authors envision Cas9 as a powerful tool for engineering living systems.