STARD8 (StAR-related lipid transfer domain containing 8) is an X-linked Rho-GTPase-activating protein that accelerates GTPase activity of RHOA and CDC42 while stimulating phosphatidylinositol 4,5-bisphosphate hydrolysis by PLCD1 1. These molecular functions regulate actin cytoskeleton organization and Rho protein signal transduction 2. STARD8 functions as a tumor suppressor across multiple cancer types. In gastric cancer, STARD8 is significantly downregulated and its decreased expression correlates with advanced TNM stage, lymph node metastasis, and poor differentiation 34. In prostate cancer, STARD8 suppresses cell proliferation, migration, and invasion by negatively regulating FAK phosphorylation, while also modulating immune evasion and chemotherapeutic sensitivity 2. In colorectal cancer with high microsatellite instability, STARD8 harbors frameshift mutations that likely inactivate its tumor suppressor function 1. Beyond cancer, STARD8 mutations are implicated in 46,XY gonadal dysgenesis, suggesting dual roles in testis determination and steroidogenesis, potentially related to cholesterol metabolism in steroid synthesis 56. STARD8 also appears relevant to keratoconus pathogenesis as a cytoskeleton-organizing protein 7 and has differential methylation in esophageal atresia 8. Clinically, STARD8 represents a promising biomarker for cancer prognosis and therapeutic target.