DOCK2 in Disease: Emerging Insights and Research Advances.

[BACKGROUND] This review aims to synthesize the structural and functional characteristics of DOCK2, as well as its mechanistic roles in various diseases, in order to provide a theoretical foundation for targeted therapies.

[METHODS] We systematically reviewed existing literature to summarize the molecular features and expression patterns of DOCK2, its regulation of cellular processes through both Rac-dependent and Rac-independent pathways, and its implications in inflammation, cancer, fibrosis, and related disorders.

[RESULTS] DOCK2, a member of the Dock-A subfamily of GEFs, is widely expressed across tissues and prominently in immune cells (e.g., dendritic cells, macrophages, T cells, B cells), where it regulates proliferation, differentiation, migration, and cytokine secretion primarily via Rac activation. Emerging evidence also links DOCK2 to non-immune cell types such as glial cells and vascular smooth muscle cells, highlighting its relevance in immune-related and broader pathological conditions including inflammatory diseases, cancer, atherosclerosis, idiopathic pulmonary fibrosis, and obesity.

[CONCLUSION] As a critical GEF, DOCK2 plays a central role in immune and non-immune cellular processes through Rac and non-Rac signaling pathways. Dysregulation of DOCK2 is closely associated with multiple diseases. Further elucidation of its regulatory networks may reveal novel therapeutic targets for treating related disorders.