RHOH is an atypical Rho family GTPase restrictively expressed in hematopoietic cells that functions as a negative regulator of cell growth and survival 1. Unlike canonical Rho GTPases, RHOH lacks intrinsic GTPase activity and remains constitutively GTP-bound due to absence of critical amino acids required for GTP hydrolysis 23. RHOH is essential for T cell development and TCR signaling, mediating recruitment and activation of ZAP70 to enable phosphorylation of the LAT signalosome during pre-TCR and TCR signaling 4. This function is critical for beta-selection, positive selection, and thymocyte maturation 3. Additionally, RHOH inhibits activation of NF-κB by TNF and suppresses activities of other small GTPases including RAC1, RHOA, and CDC42 3. RHOH deficiency causes combined immunodeficiency with severe T cell lymphopenia, impaired TCR signaling, and susceptibility to persistent viral infections including epidermodysplasia verruciformis-associated HPV 45. Aberrant RHOH expression is implicated in B cell malignancies and immune-related diseases including systemic lupus erythematosus and psoriasis 3. In acute myeloid leukemia, reduced RHOH expression correlates with increased recurrence rates, suggesting prognostic significance 6.