Additionally, eight lysosomal hub genes were identified, including Ctsd, Ctsk, Ctsb, Ctsa, Pld3, Tpsab1, Lgals3 and Smpdl3a; among them, serum protein levels of CTSD, CTSB, and LGALS3 were significantly elevated in CHD patients with irreversible PAH compared to those with reversible PAH.<h4>Conclusion</h4>This study identified dysfunctional lysosome in irreversible PAH, and the loss of compensation for lysosomal trafficking and sorting may be associated with a switch from reversible to irreversible PAH, thus providing novel insights into the molecular mechanisms underlying irreversible PAH. This evidence concerns the gene PLD3 and coronary artery disorder.