An imbalance between M1 and M2 macrophages has been noted in monocyte-derived macrophages from PAH patients.170 Previous research indicated that JNK phosphorylation promotes M1 polarization while inhibiting M2 polarization in macrophages.171 However, Zhang et al. discovered that tumor M2 macrophages over-expressing NOX4 exhibited increased JNK activity, leading to the expression and release of HB-EGF, which promotes non-small cell lung cancer proliferation in vitro.172 This suggests that the regulatory role of JNK in macrophage activation may also be relevant in the context of PAH. The gene discussed is NOX4; the disease is pulmonary arterial hypertension.