GZMB and neoplasm: This was associated with increased intratumoral infiltration of CD8+ and CD4+ T cells, elevated Granzyme B levels, and enhanced activation markers on CD8+ T cells within the tumor microenvironment.<h4>Conclusion</h4>Our study identifies PLSCR3 as a previously unrecognized negative regulator of mtDNA-associated cGAS-STING activation in CRC.