DENND10 is a guanine nucleotide exchange factor (GEF) that regulates late endocytic pathway homeostasis by activating RAB27A and RAB27B small GTPases, converting them from their inactive GDP-bound to active GTP-bound forms 1. As a core component of the 16-protein Commander complex, DENND10 functions within a multiprotein assembly that coordinates endosomal recycling and intracellular transport 21. The Commander complex, scaffolded by CCDC22 and CCDC93 coiled-coil proteins and including the Retriever subcomplex, is essential for endosomal cargo trafficking and cell homeostasis 3. Beyond canonical endosomal functions, DENND10 plays a previously underappreciated role in cancer progression by regulating extracellular vesicle (EV) biogenesis and release 4. DENND10 depletion impairs endolysosomal trafficking, reducing EV secretion and altering their composition—particularly affecting extracellular matrix and adhesion molecules—which consequently diminishes cancer cell migration, invasion, and metastatic potential 4. DENND10 expression correlates with poor prognosis in multiple cancer types, positioning it as a potential therapeutic target for metastasis prevention 4.