Ccdc93, the coiled-coil domain-containing 93 gene, is a key component of the CCC (COMMD/CCDC22/CCDC93) complex. This complex is involved in endosomal recycling of transmembrane cargos, a crucial process for maintaining cellular homeostasis. It is part of the larger Commander complex, which also includes the Retriever sub-complex and is linked to multiple cellular functions such as cell cycle and immune response [1,4,5].

Genetic studies in a Chinese population identified a coding variant in Ccdc93 (rs33975708, c.535C>T, p.Arg179Cys) associated with increased central systolic blood pressure (cSBP). Nuclease technology-mediated Ccdc93 loss in mice showed that homozygous deletion was lethal during embryonic development, while heterozygous Ccdc93+/- mice had elevated SBP, impaired arterial relaxation, and mitochondrial dysfunction, with altered fatty acid and mitochondrial metabolism [2]. In another study, a common variant in Ccdc93 (p.Pro228Leu) was associated with lower plasma low-density lipoprotein cholesterol (LDL-c) levels, lower risk of myocardial infarction (MI), and cardiovascular mortality. Ccdc93 ablation in cells reduced LDL uptake due to decreased LDL-receptor (LDLR) levels at the cell membrane, indicating its role in LDLR endosomal trafficking [3].

In conclusion, Ccdc93 plays essential roles in endosomal cargo recycling, which impacts processes like arterial function and lipid metabolism. Mouse models with Ccdc93 loss-of-function have revealed its significance in blood pressure regulation, mitochondrial function, and cardiovascular disease, highlighting its potential as a therapeutic target in these disease areas.