The development of infectious diseases represents an outcome of dynamic interactions between the disease-producing agent's pathogenicity and the host's self-defense mechanism. Proteases secreted by pathogenic microorganisms and protease inhibitors produced by host species play an important role in the process. This review aimed at summarizing major findings in research on pathogen proteases and host protease inhibitors that had been proposed to be related to the development of mollusk diseases. Metalloproteases and serine proteases respectively belonging to Family M4 and Family S8 of the MEROPS system are among the most studied proteases that may function as virulence factors in mollusk pathogens. On the other hand, a mollusk-specific family (Family I84) of novel serine protease inhibitors and homologues of the tissue inhibitor of metalloprotease have been studied for their potential in the molluscan host defense. In addition, research at the genomic and transcriptomic levels showed that more proteases of pathogens and protease inhibitor of hosts are likely involved in mollusk disease processes. Therefore, the pathological significance of interactions between pathogen proteases and host protease inhibitors in the development of molluscan infectious diseases deserves more research efforts.
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