RHOA is a small GTPase that functions as a central regulator of cytoskeletal dynamics and multiple signal transduction pathways 1. It controls diverse cellular processes including cell migration, adhesion, proliferation, and survival 1. RHOA operates through downstream effector proteins, particularly Rho kinases (ROCKs), which modulate smooth muscle contractility and vascular function 2. Additionally, RHOA regulates mitochondria-endoplasmic reticulum contact sites (MERCS) by modulating the VAPB/PTPIP51 tethering complex, thereby influencing calcium homeostasis and cellular metabolism 3. RHOA also serves as an auxiliary subunit for the TRPV4 ion channel, constraining channel gating through state-dependent interactions 4. Deregulated RHOA activity is implicated in multiple pathological contexts. In hematological malignancies, both gain and loss-of-function mutations occur, with context-dependent tumor-promoting or suppressive effects 1. Aberrant RhoA signaling contributes to neurodegenerative diseases including Parkinson's, Alzheimer's, Huntington's disease, and amyotrophic lateral sclerosis 5. Disease alleles in RHOA, CUL3, and VAPB disrupt MERCS regulation, linking RhoA dysfunction to cancer, hyperkalemia, and neurodegeneration 3. RhoA/ROCK signaling abnormalities also contribute to cardiovascular disease, particularly hypertension 2. These diverse functions establish RHOA as an attractive therapeutic target for multiple diseases.