CCDC180 (coiled-coil domain containing 180) is a coiled-coil domain protein present in extracellular exosomes with emerging roles in disease pathophysiology. In familial intracranial aneurysm (IA), a rare p.Arg979Trp variant in CCDC180 was identified through genome-wide linkage analysis in a Dutch family with multiple IA cases; however, this variant showed no association with IA status in a large general population cohort of 937 patients and 1046 controls 1. In hepatocellular carcinoma development, CCDC180 was identified as a key gene in microcystin-LR-induced malignant transformation of hepatocytes, with its expression regulated by both DNA methylation and microRNA networks 2. Most notably, CCDC180 functions as a novel immunohistochemical marker for liposarcoma, showing high accuracy in differentiating atypical lipomatous tumors/well-differentiated liposarcoma (ALT/WDL) from benign lipomas 3. Functionally, CCDC180 knockdown inhibits liposarcoma cell proliferation, while CCDC180 expression suppresses cell migration, invasion, and apoptosis resistance in WDL cells, with expression inversely associated with adipogenic differentiation 3. These findings suggest CCDC180 contributes to malignant potential in liposarcoma, though its precise molecular mechanisms require further characterization.