Microtubules have long been regarded as structural scaffolds that maintain cell shape, mediate intracellular transport, and drive cell division. Over the past two decades, this view has shifted, with accumulating evidence demonstrating that microtubules are dynamic and active participants in cellular signaling networks, regulating key physiological processes such as cell survival and differentiation through multiple mechanisms. Recently, the team led by Michel O. Steinmetz reported in Cell the first structural elucidation of how microtubules regulate immune responses by "sequestering and releasing" the guanine nucleotide exchange factor GEF-H1 protein. This work addresses a central question in microtubule-mediated signal transduction, provides a conceptual and methodological framework for basic research, and offers new targets and strategies for cancer immunotherapy and targeted drug development.