Here, we focus on: (i) the seminal studies that led investigators to identify Dsg3 and 1 as targets of pathogenic autoAbs, and how these studies shaped our understanding of disease, and (ii) the identification of non-Dsg autoAbs, with a particular focus on the contribution of comprehensive autoAb profiling facilitated by protein microarray technology, as well as the potential role of these autoAbs in disease, and how these findings may re-shape/direct how we ultimately view the pathogenesis of PV. This evidence concerns the gene DSG3 and acquired polycythemia vera.