A study by Perez et al., using whole-exome sequencing, identified genes implicated in IPAH and revealed that topoisomerase-II binding protein 1 (TOPBP1), which is crucial for DNA damage response and replication, was downregulated in pulmonary microvascular endothelial cells (PMVECs) from IPAH patients, resulting in increased DNA damage and apoptosis (241). Here, TOPBP1 is linked to idiopathic pulmonary arterial hypertension.