This observation is not akin to the reduced penetrance observed in genetic mouse models of Bmpr2 deficiency, which represents the major cause of PAH in humans.33–35 In future, it would be interesting to explore the impact of disease-promoting stimuli on PAH and the polyamine pathway in Atp13a3P452Lfs variant mice. This evidence concerns the gene BMPR2 and pulmonary arterial hypertension.