LDLR and familial hypercholesterolemia: •Functional analysis using single-cell assays revealed that three LDLR variants (p.Asp221Gly, p.Gly592Glu, p.Tyr828Phefs∗101) show impaired receptor activity due to reduced expression, ligand binding, internalization defects, or a stop-loss function, supporting their pathogenic role in familial hypercholesterolemia.