Mmp9, also known as matrix metalloproteinase 9, is a zinc-dependent proteolytic metalloenzyme belonging to the gelatinase B subgroup of the MMPs family. It is involved in extracellular matrix (ECM) remodeling and is associated with numerous pathological conditions [3]. Mmp9 has been linked to pathways like NFκB/VEGF/MMP9 in diabetic retinopathy-linked dementia [5].

In the context of cancer, pharmacologic or genetic targeting of Mmp9 (akin to gene knockout in models) significantly reduced metastatic cell penetration across the blood-brain barrier and limited micrometastasis formation, suggesting its role in brain metastasis [1]. In pancreatic cancer, MMP9 levels were elevated from the T2 stage, indicating its potential as a biomarker for late-stage disease detection [2]. In esophageal cancer, a protein complex of LCN2, LOXL2 and MMP9 promoted tumour metastasis, and targeting this complex could be a therapeutic strategy [6].

In the context of other diseases, the CT genotype of the MMP9-1562C>T polymorphism was strongly associated with the risk of developing atherosclerosis [4]. In systemic lupus erythematosus, the MMP9 promoter was significantly hypomethylated in patients, highlighting its potential as a diagnostic biomarker [7].

In conclusion, Mmp9 plays crucial roles in multiple biological processes and disease conditions, especially in cancer metastasis, atherosclerosis, and autoimmune diseases. Studies using gene-targeting approaches (similar to KO/CKO mouse models) have revealed its significance in these disease areas, providing insights into potential therapeutic targets and diagnostic biomarkers.