COMMD1 is a multifunctional scaffold protein essential for endosomal recycling of transmembrane cargo as a core component of the Commander complex 1. The Commander complex comprises the CCC subcomplex (containing COMMD1-COMMD10 and CCDC proteins) and the Retriever subcomplex, functioning in coordinated cargo trafficking 1. COMMD1 regulates copper homeostasis by facilitating ATP7A trafficking between the trans-Golgi network and peripheral vesicles, with mutations in COMMD1 associated with hepatic copper accumulation in Bedlington terriers 2. The protein modulates cullin-RING E3 ubiquitin ligase complexes by displacing CAND1, promoting ubiquitination of key substrates including NF-κB subunit RELA, leading to its proteasomal degradation and suppression of inflammatory signaling 3. COMMD1 regulates sodium channel trafficking and epithelial ion transport through ubiquitination-dependent mechanisms affecting ENaC and CFTR expression 4. Additionally, COMMD1 inhibits HIF-1α-mediated transcription by preventing its dimerization with HIF-1β, suppressing tumor invasion and metastasis 5. Recent studies reveal COMMD1's role in copper-dependent cell death (cuproptosis), with triptolide inducing cervical cancer cell death through the XIAP/COMMD1/ATP7A/B axis 6. A COMMD1 polymorphism (rs11125908) associates with rheumatoid arthritis susceptibility 7.