Background:We detected autoantibodies against a new complex cell junction, the area composita of the heart [an intricate cell junction that includes the protein Myocardial Zonula Adherens Protein (MYZAP, AKA MYOZAP)] in patients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia, South America (El Bagre-EPF).Methods: We aimed to study if MYZAP was expressed in the skin, and, if so, its relationship with El Bagre-EPF autoantigens.We utilized a case-control study, testing 43 patients and 43 controls from the endemic area matched by demographics, age, gender, living place, and work activities using multiple immunological methods.Results: MYZAP is expressed in the human skin (epidermis and dermis), as well in the skin appendages, their neurovascular supply structures, and neural receptors (in all of these sites, mostly in the cells junctions).MYZAP present in the cell membranes, and is also located in intracytoplasmic and nuclear regions.All El Bagre-EPF patient autoantibodies perfectly colocalized with MYZAP (a commercial antibody from Progen Biotechnik, Heidelberg, Germany) in the skin (p< 0.01).Conclusion: We describe for the first time in the medical literature the expression of a new protein MYZAP in several structures in the skin, colocalizing with El Bagre-EPF autoantigens and suggesting that further studies could focus on the putative roles of this molecule in the skin.