The symbiotic interaction between cnidarians, such as corals and sea anemones, and the unicellular algae Symbiodinium is regulated by yet poorly understood cellular mechanisms, despite the ecological importance of coral reefs. These mechanisms, including host-symbiont recognition and metabolic exchange, control symbiosis stability under normal conditions, but also lead to symbiosis breakdown (bleaching) during stress. This study describes the repertoire of the sterol-trafficking proteins Niemann-Pick type C (NPC1 and NPC2) in the symbiotic sea anemone Anemonia viridis. We found one NPC1 gene instead of two in vertebrates. While only one NPC2 gene is present in most metazoans, this gene has been duplicated in cnidarians and we detected four NPC2 genes in A. viridis. However, only one gene (AvNPC2-d) was upregulated in symbiotic sea anemones and displayed higher expression in the gastrodermis (symbiont-containing tissue) than in the epidermis. We performed immunolabeling experiments on tentacle cross sections and demonstrated that the AvNPC2-d protein was closely associated with symbiosomes. In addition, AvNPC1 and AvNPC2-d gene expression was strongly downregulated during stress, especially at the onset of symbiosis breakdown. These data suggest that AvNPC2-d is involved in both the stability and dysfunction of cnidarian-dinoflagellate symbioses.