Mechanistically, KLRB1 may influence MDD through two plausible pathways: (1) modulating microglial activation and neuroinflammation, as KLRB1+ immune cells have been shown to infiltrate the brain during chronic stress, promoting proinflammatory cytokine release (Winans et al., 2023); and (2) interfering with the hypothalamic-pituitary-adrenal (HPA) axis (Wei and Hong, 2024), given KLRB1’s role in stress-induced immune dysregulation. Here, KLRB1 is linked to major depressive disorder.