T-cell activation Rho GTPase-activating protein (TAGAP)

T-cell activation Rho GTPase-activating protein (TAGAP) is a member of the Rho GTPase-activating protein family, predominantly expressed in activated T cells, where it regulates RhoA activity and is implicated as a critical modulator of T-cell signaling, differentiation, and immune activation. Genome-wide association studies have identified TAGAP genetic variants as risk factors for several autoimmune diseases, including inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and celiac disease, likely through its effect on Th17 pathway regulation and gut antimicrobial defense. TAGAP influences both the adaptive and innate immune responses, with deficiency or altered expression leading to pathogenic immune cell polarization, impaired antimicrobial peptide production, microbiota imbalance, and increased susceptibility to autoimmune and inflammatory diseases. Experimental therapies in animal models—including anti-p40 antibodies and reg3g replacement—suggest TAGAP-associated pathways are druggable, but clinical relevance and safety in humans are yet to be established.

Other names

TAGAP1FKSG15FLJ32631IDDM21ARHGAP47T-cell activation GTPase-activating protein

Modulation of TCR (T-cell receptor) signaling; Regulation of Th17 differentiation; Enhancement or inhibition of antimicrobial peptide expression