RHOU is an atypical Rho family GTPase that functions as a key regulator of cell morphology and migration. Unlike classical Rho GTPases, RHOU has no detectable GTPase activity but exhibits high intrinsic guanine nucleotide exchange activity, suggesting it remains constitutively GTP-bound. RHOU activates protein kinase PAK1 and controls cell migration through regulation of focal adhesion assembly, cytoskeletal organization, and actin remodeling. It also promotes cell-cycle re-entry in quiescent cells. RHOU requires PAK4-mediated stabilization to resist ubiquitination and maintain protein expression levels, and functions through homodimer formation involving its C-terminal palmitoylation domain 12. Recent evidence reveals that RHOU plays a role in senescence-associated inflammation: RHOU expression, regulated by the mechanosensors GATA4 and YAP, drives actin cytoskeleton remodeling necessary for cell enlargement and the senescence-associated secretory phenotype (SASP) in aging adipose tissue 3. In cancer, RHOU expression is upregulated in prostate cancer and invasive pituitary adenomas, where it promotes migration, invasion, and metastatic phenotypes 42. RHOU induction occurs downstream of both STAT3 and non-canonical Wnt signaling, linking it to pathways implicated in tumor progression. These findings position RHOU as an emerging biomarker and potential therapeutic target in cancer metastasis and age-related inflammatory pathologies, though specific therapeutics targeting RHOU have not yet been clinically developed.