Rare diseases represent an important public-health issue, affecting 26-30 million persons across Europe, and a major challenge for research. The fragmentation of resources and knowledge for the 6000-8000 rare diseases and the lack of treatment for the majority of them necessitate a coordinated European approach to unravel the underlying molecular defects and pathophysiological mechanisms. The low number of affected patients requires transnational collaboration with multidisciplinary approaches to map prevalences, build patient registries, identify biomarkers, develop new diagnostics and finally perform clinical studies for the development of treatments. The successful linking of research funding organisations in E-Rare-1 and the subsequent exemplary joint funding activities have attested the need of, and the acknowledgment from, the research community for transnational funding of collaborative, multidisciplinary and ambitious projects on rare diseases. It has leveraged funding for rare disease research in countries without specific programmes for rare diseases and thus enabled the participation of researchers in these countries to transnational projects. The E-Rare-2 project aims at deepening and extending the cooperation among the E-Rare-1 and the five new partners by systematic exchange of information, yearly launching of joint calls, thorough assessment of the funding mechanisms and results of the funded research projects and, finally, strategic activities aiming at a sustainable development and extension of the network. Special attention will be given to the outreach and knowledge exchange with new member states, countries outside of Europe and key stakeholders/initiatives important for rare diseases. E-Rare-2 activities will thus further contribute to reducing fragmentation of research and resources through the enhanced coordination and transnational funding of excellent research on rare diseases, thereby shaping the European Research Area for rare diseases.