HCQ exerts its immunomodulatory effects through multiple mechanisms: (1) alkalinization of endolysosomes blocks proteolytic maturation of TLR9/7 and prevents ligand binding [17]; (2) HCQ more effectively suppresses IL-6 secretion and subsequent Gd-IgA1 and IgG-IgA immune complex formation compared to competitive TLR9/7 inhibitors like ODN2088 [50]; and (3) by reducing IL-6 production, HCQ rebalances the Th17/Treg ratio [65], thereby mitigating chronic inflammation and endothelial dysfunction [51]. The gene discussed is TLR9; the disease is endothelial dysfunction.