Under inflammatory conditions associated with PAH, granzyme B cleaves ITSN and generates the EHITSN, a biologically active protein fragment, present in ECPAH and human lung tissue with plexiform lesions; its expression triggers EC proliferation and selection of a proliferative/plexiform EC phenotype leading to formation of complex pulmonary vasculopathy in a murine model (Patel et al., 2013, 2017). Here, ITSN1 is linked to pulmonary arterial hypertension.