Colorectal cancer (CRC) stands as the third most prevalent cancer type, contributing significantly to cancer-related deaths. CRC develops through the sequential acquisition of somatic mutations in APC, KRAS and TP53 leading benign tumors to evolve into aggressive malignancies. Most CRCs follow the chromosomal instability (CIN) pathway, characterized by an increased rate of chromosomal rearrangements, although the molecular bases are not well understood. Long interspersed element-1 (L1) is a type of transposon capable of causing insertional mutagenesis and DNA damage. Elevated L1 activity has been associated with CRC, contributing to genomic instability and serving as a potential biomarker. However, the functional contributions of L1 in CRC, particularly during the early stages of tumorigenesis remain poorly understood, mostly because experimental models studying L1 function are scarce or nonexistent. Thus, there is a need to define the timing and mechanisms by which retrotransposition influences the early steps of CRC. To pursue this goal, I am establishing 2D and 3D models representing colorectal cancer initiation and progression to manipulate L1 expression and determine its function in CRC biology. Elucidating the functional role of L1 in CRC initiation and progression will provide valuable insights into the molecular mechanisms underlying CRC development. Understanding the interplay between L1 and key genetic events in CRC could potentially open new avenues for diagnostic and therapeutic strategies in combating colorectal cancer.