MFHAS1 is a multifunctional GTP-binding protein that serves as a critical regulator of innate immune signaling and cellular differentiation. Primary function involves modulating Toll-like receptor (TLR) signaling: MFHAS1 negatively regulates TLR4-mediated AP-1 activation by retaining PP2A phosphatase in the cytoplasm 1, while displaying biphasic effects on TLR2 signaling with inhibitory effects at 6 hours and stimulatory effects after 24 hours through JNK and p38 MAPK activation 23. Beyond immune regulation, MFHAS1 promotes M1 macrophage polarization via STAT6/KLF4 pathways in colorectal cancer progression 4 and attenuates high-glucose-induced inflammation through Akt/HO-1 signaling in endothelial cells 5. MFHAS1 also participates in erythrocyte differentiation via ERK1/2 activation. Disease relevance is substantial: elevated MFHAS1 levels associate with sepsis 2, genetic variants near MFHAS1 link to periodontitis susceptibility 6, systemic lupus erythematosus 7, autism spectrum disorder 8, and lymphoma progression 9. Clinically, MFHAS1 suppression induces breast cancer cell pyroptosis through JNK/NF-κB/caspase-1/GSDMD signaling, positioning MFHAS1 as a potential therapeutic target 10.