Since the demonstration nearly 20 years ago that mutations of bone morphogenic protein receptor 2 (BMPR2) are associated with heritable pulmonary arterial hypertension [1–4], investigators have postulated that altered BMPR2 signalling, whether inherited or acquired, may be a novel therapeutic target for pulmonary arterial hypertension (PAH) of all aetiologies. Enhancing BMPR2 activity in animal models of pulmonary hypertension attenuates the severity of pulmonary vascular growth and proliferation [5, 6], although these models have not been predictive of responses in human disease. In the current issue of the European Respiratory Journal, Spiekerkoetter et al. [7] report that BMPR2 mRNA expression is attenuated in PAH and that FK506 (tacrolimus), a BMPR2 activator, produced no meaningful effects in a small, single-centre 16-week clinical trial in subjects with PAH due to a variety of aetiologies. While the authors identified several “FK506 responders” in a post hoc analysis, they found no difference in BMPR2 expression between “responders” and “non-responders”, nor did they observe any change in serologic biomarkers linked to increased BMPR2 signalling.