Anthropogenic drivers and global warming are altering the occurrence of infectious marine diseases, some of which produce mass mortalities with considerable ecosystemic and economic costs. The Mediterranean Sea is considered a laboratory to examine global processes, and the fan mussel Pinna nobilis a sentinel species within it. Since September 2016, fan mussels suffer a die-off, very likely provoked by the protozoan Haplosporidium pinnae. Population dynamic surveys, rescue programmes, larvae collector installation and protection of infected adults from predators, have increased knowledge about the factors conditioning the spread of the die-off; previous model simulations indicate that water temperature and salinity seem to be related to the manifestation of the disease, which at the end are strongly influenced by climate change and anthropogenic actions. The absence of natural recruitment implies that fan mussel populations are not recovering, but the survival of populations living in paralic environments provides an opportunity to study the disease and its conditioning factors. The present situation is proposed as an example of what is to come in the global context of climate change and poses several questions: are we the witnesses of the potential extinction of a sentinel species? Can we avoid the potential extinction of this species by applying active measures, and which measures will be more effective? How many other more overlooked species might experience a massive and unnoticed die-off before it is too late to implement any preservation action? For the extinction of community structure species will provoke unpredicted ecological cascade effects with global implications.