RHOG (ras homolog family member G) is a small GTPase that functions as a critical regulator of cytoskeletal dynamics, lymphocyte cytotoxicity, and cell signaling. As a GTPase, RHOG cycles between inactive GDP-bound and active GTP-bound states, with its activation mediated by guanine nucleotide exchange factors (GEFs) such as Trio and the DOCK/ELMO complex 1. RHOG's primary mechanism involves orchestrating actin cytoskeleton reorganization and coordinating the activation of downstream GTPases, particularly Rac1, through interaction with DOCK5/ELMO1, where RhoG facilitates a conformational transition from closed to open states that enhances GEF activity 2. In lymphocytes, RHOG serves essential functions in cytotoxic granule exocytosis by maintaining granule docking at the plasma membrane through interaction with Munc13-4 3, and regulates gene expression including interferon-gamma and NFAT-dependent transcription 4. Clinically, RHOG deficiency causes hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory disorder characterized by severely impaired cytotoxic T cell and natural killer cell function 35. Conversely, RHOG knockout in CAR T cells unexpectedly enhances therapeutic efficacy, suggesting therapeutic potential for engineered cell-based immunotherapies 6. RHOG also participates in phagocytosis through Rac1-mediated pathways in trabecular meshwork cells 7.