COMMD9 is a scaffold protein within the Commander complex essential for endosomal recycling of transmembrane cargos 1. The Commander complex comprises CCC and retriever subcomplexes that organize SNX17-dependent recycling of integral membrane proteins containing ΦxNPxY/F sorting motifs 1. COMMD9 specifically regulates epithelial sodium channel (ENaC) surface expression by modulating Na+ transport in kidney collecting ducts, functioning as an endogenous ENaC regulator 2. Additionally, COMMD9 promotes TFDP1/E2F1 transcriptional activation in non-small cell lung cancer, where it is upregulated and drives cancer cell proliferation and migration 3. COMMD9 controls Notch receptor recycling through the CCC complex; its deletion causes embryonic lethality with cardiovascular alterations mimicking Notch deficiency 4. In copper homeostasis, COMMD9 deficiency destabilizes the entire CCC complex, resulting in hepatic copper accumulation under high-copper diets by impairing ATP7B endosomal recycling 5. Mutations in COMMD9 cause Ritscher-Schinzel syndrome, a congenital malformation syndrome presenting with cerebellar, cardiac, craniofacial, and kidney dysfunction due to disrupted Commander assembly and reduced cell surface presentation of development-critical proteins 1. COMMD9 expression correlates with immune cell infiltration in sepsis pathogenesis 6, suggesting broader roles in inflammatory and immune responses.