DNA damage and repair encompass a range of alterations and mutations in DNA, serving as a crucial mechanism for maintaining genome stability in tumor cells.1 Abnormal expression of oncogenes or tumor suppressors caused by the dysregulation of DNA damage and repair is connected to tumor proliferation, metastasis, and immune microenvironment.2 Telomere maintenance 2-interacting protein 1 (TTI1), a regulator of DNA damage and repair, is expressed in numerous organisms and is assumed to play a central role in regulating a wide spectrum of DNA damage responses, telomere maintenance, and checkpoint signaling.3 TTI1 was regarded as an oncogene and promoted tumor proliferation in colorectal cancer (CRC), providing preliminary evidence for the significance of TTI1 in CRC.4 Nevertheless, the precise role of TTI1 in CRC remains unclear. Therefore, we conducted a comprehensive investigation of TTI1 expression in CRC and its associations with clinical significance, prognosis, molecular mechanisms, tumor immunity, and potential clinical value. In summary, our study identified TTI1's role in CRC and its immune microenvironment, highlighting its significance in metastasis and immunotherapy, with meta-chlorophenylpiperazine (mCPP) identified as a potential modulator.