The low-density lipoprotein receptor (LDLR) is responsible for the uptake of cholesterol-containing lipoprotein particles into cells(1,2). The amino-terminal region of LDLR, which consists of seven tandemly repeated, similar to 40-amino-acid, cysteine-rich modules (LDL-A modules), mediates binding to lipoproteins(3,4). LDL-A modules are biologically ubiquitous domains, found in over 100 proteins in the sequence database(5). The structure of ligand-binding repeat 5 (LR5) of the LDLR, determined to 1.7 Angstrom resolution by X-ray crystallography and presented here, contains a calcium ion coordinated by acidic residues that lie at the carboxy-terminal end of the domain and are conserved among LDL-A modules. Naturally occurring point mutations found in patients with the disease familial hypercholesterolaemia(6) alter residues that directly coordinate Ca2+ or that serve as scaffolding residues of LR5.