HLA-G and atrial fibrillation: HLA-G lacks direct links to AF but may contribute to AF pathogenesis via MAM-mediated mechanisms—aligning with our GSEA results associating it with immune and calcium-related pathways: Mechanistically, soluble HLA-G (sHLA-G) interacts with CD8+ T cells via the CD8 coreceptor, triggering Fas/Fas-ligand-mediated apoptosis and inducing extracellular calcium influx (Puppo et al., 2002).