Matrix Metalloproteinases (MMPs) are the most important enzymes for Extracellular matrix maintenance. MMPs are also involved in several biological and pathological diseases. They are a great challenge for science due to its high complexity in regulation and activity. MMPs are regulated by EMMPRIN through paracrine manner or through cell-to-cell interaction. Cyclophilin A (CyPA) expression is correlated with MMP-1, MMP-2 and MMP-9 expression in inflamed gingiva. CyPA plays an important role in biological conditions like T-cell activation, protein folding and trafficking. Understanding its role in the development of diseases and its mode of action requires more studies.