IGFBP-5 is a context-dependent regulator of ECM remodeling via IGF-independent interaction with PAI-1 and modulation of fibrinolytic activity. It is generally pro-fibrotic in PAH models but may exert anti-apoptotic effects in specific contexts. and It represents a promising but complex therapeutic target. This evidence concerns the gene IGFBP5 and pulmonary arterial hypertension.