This issue is the subject of intense research, as different experimental and theoretical approach models have emerged to clarify the mechanism of acantholysis; presently, the most accepted notion is that the main mechanism of pemphigus vulgaris blistering is the direct steric interference of homophilic and heterophilic Dsg:Dsg and Dsc:Dsg binding caused by pemphigus autoantibodies [20,21,22]. This evidence concerns the gene DSG1 and pemphigus.