Corneal disease is responsible for the main cause of bilateral blindness in the world, second only to cataract. As an essential actin binding protein, destrin mutation often result in cytoskeleton dynamics abnormalities in corneal epithelial surface, and thus, cause corneal epithelial cell hyperproliferation, inflammation, and angiogenesis, namely, corneal diseases. In this study, we explored the interaction and crosstalk between pathways in response to destrin mutation. As we expected, the results showed that regulation of actin cytoskeleton was the significant pathway in destrin mutation mice. Further analysis indicated that there were 28 significant pathways crosstalk to pathway of regulation of actin cytoskeleton. Importantly, three pathways, including regulation of actin cytoskeleton pathway, pathway in cancer, and B cell receptor signaling pathway were linked by inositol phosphate metabolism in crosstalk analysis of GO relationships among pathways. All of them have been demonstrated to play important roles in cytoskeleton dynamics. We deeply hope that our study could provide insights into cytoskeleton dynamics abnormalities in destrin mutation corneal disease. Key words: ADF/cofilin, cytoskeleton dynamics, pathway crosstalk.