In PAH, dysfunctional bone morphogenetic protein type II receptor (BMPR-II)-mediated signalling impairs the SMAD1/5/8 pathway (Gomez-Puerto et al., 2019), whilst the overactive TGF-β pathway results in a dysregulated SMAD2/3 pathway leading to abnormal transcriptional activation of target genes (e.g., Id1 for BMP and Pai1 for TGF-β) (Tie et al., 2022). The gene discussed is SMAD1; the disease is pulmonary arterial hypertension.