Apolipoprotein E (Apo E) is involved in lipid metabolism and plays a crucial role in maintaining the balance of lipoprotein interactions within the body. Mutations in the Apo E protein have been associated with Hyperlipoproteinemia type III, which is characterized by abnormal lipid accumulation in the body. This work explores the structural and functional consequences of seven missense mutations (R154C, R154S, R160C, R163C, R163H, K164E, and K164Q) of Apo E protein associated with Hyperlipoproteinemia type III. Through computational methods such as homology modelling, pathogenicity prediction, Molecular docking and Molecular dynamics, we have investigated the impact of single-point mutations on protein structure, stability, and dynamics. Molecular dynamics simulation studies of wild type Apo E and modelled mutants provided insights into the conformational changes and flexibility of Apo E mutants, giving insights into mechanistic aspect of the influence of mutations on the receptor binding domain and protein structure. The results demonstrate that most of the studied mutations disrupt critical stabilizing interactions and alter domain flexibility thus destabilizing the protein structure and function affecting its interaction with Low-Density Lipoprotein receptor 1 (LDLR1). These molecular insights into how the mutations affect Apo E's conformation and its interaction with the LDL receptor 1 (LDLR1) will help to contribute to a deeper understanding of the pathogenesis of Hyperlipoproteinemia type III.