CABLES2 (Cdk5 and Abl enzyme substrate 2) is a protein with emerging roles in cell cycle regulation and embryonic development. CABLES2 belongs to the CABLES protein family and interacts with cyclin-dependent kinases (CDK3, CDK5) and c-ABL 1. The protein is ubiquitously expressed across adult mouse tissues, with particularly high expression in brain, testis, ovary, and corpus luteum 1. Functionally, CABLES2 appears critical for cell cycle progression. Complete disruption of the Cables2 locus causes embryonic lethality through growth retardation and enhanced apoptosis at gastrulation, involving p53 pathway activation and reduced expression of the neighboring Rps21 gene 2. Downregulation of CABLES2 decreases expression of cell cycle progression genes (CDCA3, CDCA8, CDC25B) and promotes apoptosis 3. Clinically, CABLES2 is implicated in colorectal cancer (CRC) susceptibility. Genetic variants affecting CABLES2 promoter activity are associated with increased CRC risk 4, and knockdown experiments confirm CABLES2's vital role in colorectal carcinogenesis 4. CABLES2 is also associated with radiotherapy-induced proctitis and radiation response pathways 56. Additionally, CABLES2 methylation quantitative trait loci show association with CRC risk 7. These findings position CABLES2 as an important regulator of cell cycle control with relevance to cancer development and radiation response.