CUBN encodes cubilin, an endocytic receptor essential for nutrient absorption across intestinal, renal, and embryonic epithelia 1. The protein contains 27 CUB domains that bind multiple ligands including lipoproteins, vitamins, iron-transport proteins, and the cobalamin-intrinsic factor complex in a calcium-dependent manner 1. Cubilin cooperates with megalin (LRP2) and amnionless (AMN) to mediate receptor-mediated endocytosis of high-density lipoproteins, albumin, transferrin, hemoglobin, and other cargo molecules 1. The C-terminal region specifically facilitates renal albumin reabsorption 1. Functionally, CUBN variants associate with proteinuria; biallelic C-terminal mutations cause isolated albuminuria with preserved renal function, representing benign chr10 proteinuria 1. N-terminal mutations cause Imerslund-Gräsbeck syndrome, characterized by vitamin B12 malabsorption 1. The missense variant I2984V associates with increased albuminuria risk in both diabetic and non-diabetic populations 2, with 41% elevated risk for persistent microalbuminuria progression in type 1 diabetes 2. CUBN polymorphisms also associate with coronary artery disease susceptibility 3 and influence serum vitamin D levels 4. Collectively, CUBN variations modulate protein and micronutrient handling with implications for kidney disease progression and cardiovascular outcomes.