CYRI-B (CYFIP-related Rac1 interactor B, also called FAM49B) is a negative regulator of RAC1 signaling that controls cytoskeletal dynamics and immune responses. As a Rac-GTP-sequestering protein 1, CYRI-B limits RAC1-driven actin polymerization and constrains the Scar/WAVE complex, thereby regulating cell migration, chemotaxis, and epithelial polarization 2. In immune cells, CYRI-B acts as a negative regulator of CEACAM3-mediated phagocytosis; CYRI-B knockout enhances Rac GTP loading and PAK phosphorylation, increasing bacterial internalization 13. CYRI-B protects against bacterial infections including Salmonella and Mycobacterium tuberculosis by restricting macropinocytosis and phagocytosis 4. However, in pancreatic cancer, CYRI-B has complex roles: it buffers RAC1 hyperactivation in early tumorigenesis but promotes metastasis in advanced disease by facilitating lysophosphatidic acid receptor uptake via macropinocytosis 5. Additionally, CYRI-B influences cell proliferation regulation, potentially through cyclin pathways 6. A potential association with familial Parkinson's disease has been identified through copy number variation analysis, though functional relevance requires validation 7.