Fig. 1.

(a) Illustrates the five different classes for defects of LDL receptor function and the consequences of the different defects on the cell surface for class I and II defects (b) or class III defects (c). Class I mutations include null alleles with no detectable LDL receptor protein. Class II mutations produce transport-defective LDLR proteins that are either completely (class II a) or partially blocked (class II b or leaky LDLRs) in their transport from the endoplasmic reticulum to the Golgi apparatus due to impaired glycosylation. Class III mutations encode LDL receptors with normal intracellular transport but defective LDL binding. Class IV mutations produce LDL receptors with normal transport and cell surface LDL binding but defective clustering in clathrin-coated pits for internalization. Class V mutations produce recycling defective receptors that internalize normally, but are unable to release bound ligand within the acidic environment of the endosome, and thus do not recycle to the cell surface