Biomineralized structures can function as a barrier to the external environment, and as such are conceptually entwined with innate immune processes. Disentangling immune and biomineralization mechanisms represents a significant challenge to understand how organisms could integrate biomineral formation and plasticity with the maintenance of critical physical and innate immune protection. There is increasing evidence that immune proteins can serve genuine dual-functional roles, both in the regulation of biomineralization, as well as resisting pathogens. This awareness is growing in models as diverse as the dual-functioning haemocytes of marine bivalves, and mineralization/demineralization of the avian eggshell. Moreover, reef corals, in which calcification is coupled to the photosynthetic activity of their mutualistic symbionts, must adapt their innate immune system to achieve this tolerance. Cnidarian immune-related processes in response to abiotic stresses are increasingly implicated in the loss of symbiosis and coral bleaching. This Research Topic aims to collect selected contributions from the speakers and attendees to the virtual conference “Innate immunity in a biomineralized context: trade-offs or synergies?”, held on 23rd-24th of March 2021. It also aims to bring together scientists working with diverse models of biomineralization, from the little-studied perspective of innate immune function. Topics will encompass microbiota, the roles played by specific genes/proteins, cells, and all other mechanisms of defences of mineralized structures including encapsulation. We welcome the contribution of Original Research articles, Reviews and Mini Reviews which cover, but are not limited to, the following subtopics: • Innate immunity as an overarching functional theme, including osteoimmunity, immunotolerance and encapsulation. • Diverse biomineralized systems and innate immunity: o Marine bivalves / molluscs / gastropods o Avian eggshell (both unfertilized and embryonated) o Bone o Corals o Teeth • Levels of investigation: molecules, cell, tissue, structure of the mineralized structure/organism and their associated/interacting elements (supporting structures like eggshell membranes and microbiota for avian eggshells, for example) • Adaption to environmental/physiological changes (acidification/decalcification, host-microbe interactions, symbiosis, development, ageing) • Structural and molecular conservation across different animal species • Comparative biology/immunology: specific and shared mechanisms/molecules