Rare disease registries have now been recognized as a global priority for progress both in monitoring and documenting the natural course, and preventing and treating rare diseases. However, a disease registry is only one element of rare disease translational research. Here, we outline what we believe are ten key components in comprehensive rare disease translational research and describe critical relationships between them. These components are: (i)client ? practitioner partnerships; (ii)disease registries; (iii)biobanks; (iv) genomics and other-omics platforms; (v)community-based and population-wide studies; (vi)bioinformatics and high performance computing; (vii)interactions with pharma to facilitate drug discovery; (viii) personalized treatments based on geno type-pheno type correlations; (ix)eHealth and a whole of life record; and (x)regulatory frameworks, particularly with regard to specimen and data sharing, and the return of results.