Conversely, we found that SNPs in CD44 (rs12270356), COL17A (rs2282436 and rs10883962), COL3A1 (rs16830979), CTSL (rs2274611), KLK2 (rs2664156), and MMP11 (rs738791), were associated with a heightened risk of developing MDD, potentially by disrupting ECM remodeling, synaptic function, and BBB stability. The gene discussed is CTSL; the disease is major depressive disorder.