Beyond its functional relevance in animal models, a reduction of PSGL-1 in mature B-cells of iPAH patients in comparison to healthy controls was detected (Gonzalez-Tajuelo et al., 2020), indicating that PSGL-1 dysregulation on B- and plasma cells in iPAH may lead to impaired peripheral tolerance and negative selection of autoreactive B-cells, thereby promoting the development of PH (Figure 1). This evidence concerns the gene SELPLG and idiopathic pulmonary arterial hypertension.