Sjögren-Larsson syndrome (SLS) is an autoimmune disorder inherited in an autosomal recessive pattern. To date, 80 missense mutations have been identified in association with the Aldehyde Dehydrogenase 3 Family Member A2 (ALDH3A2) gene causing SLS. Disruption of the function of ALDH3A2 leads to excessive accumulation of fat in the cells, which interferes with the normal function of protective membranes or materials that are necessary for the body to function normally. We retrieved 54 missense mutations in the ALDH3A2 from the OMIM, UniProt, dbSNP, and HGMD databases that are known to cause SLS. These mutations were examined with various in silico stability tools, which predicted that the mutations p.S308N and p.R423H that are located at the protein-protein interaction domains are the most destabilizing. Furthermore, to determine the atomistic-level differences within the protein-protein interactions owing to mutations, we performed macromolecular simulation (MMS) using GROMACS to validate the motion patterns and dynamic behavior of the biological system. We found that both mutations (p.S380N and p.R423H) had significant effects on the protein-protein interaction and disrupted the dimeric interactions. The computational pipeline provided in this study helps to elucidate the potential structural and functional differences between the ALDH3A2 native and mutant homodimeric proteins, and will pave the way for drug discovery against specific targets in the SLS patients.