MMP8 (matrix metalloproteinase 8) is a zinc-dependent endopeptidase primarily produced by myeloid cells that degrades fibrillar type I, II, and III collagens and remodels the extracellular matrix 1. This collagenase plays complex roles across multiple physiological and pathological contexts. In periodontitis, MMP8 serves as a prominent salivary and gingival crevicular fluid biomarker of disease progression 123. Elevated salivary MMP8 levels correlate with progressive periodontal destruction, and non-surgical periodontal therapy significantly reduces MMP8 concentrations alongside clinical improvement 23. Circulating myeloid-derived MMP8 contributes to stress-related neuropsychiatric disorders by crossing the blood-brain barrier and remodeling extracellular space in the nucleus accumbens, driving stress-susceptible behavior 4. MMP8 depletion prevented stress-induced social avoidance, suggesting therapeutic potential. In cancer, MMP8 exhibits tissue-dependent dichotomous effects: it inhibits invasion and proliferation in breast, skin, and oral tongue cancers, protecting against metastasis, while high levels worsen prognosis in liver and gastric cancers 5. The rs11225395 polymorphism associates with reduced laryngeal squamous cell carcinoma risk 6. In diabetic wound healing, exosomal miRNA-26b-5p suppresses neutrophil extracellular traps by targeting MMP8, promoting tissue repair 7. Overall, MMP8 functions as a context-dependent regulator of tissue homeostasis with implications for inflammation, neuropsychiatry, and cancer.