Despite the revolution in functional genome analysis a wide gap in understanding associations between the (epi)genome and complex phenotypes of interest currently remains and impedes efficient use of annotated genomes for precision breeding. The BovReg consortium will provide a comprehensive map of functionally active genomic features in cattle and how their (epi)genetic variation in beef and dairy breeds translates into phenotypes. This constitutes key knowledge for biology-driven genomic prediction needed by scientific and industry livestock communities. The BovReg brings together a critical mass of experts in ruminant research and beyond encompassing bioinformatics, molecular and quantitative genetics, animal breeding, reproductive physiology, ethics and social science. Our 20 partners from the EU, Canada and Australia form a global interdisciplinary team, which builds on previous and running national and EU-funded projects and many established industry cooperations. In BovReg we will generate functional genome data based on FAANG core assays from representative bovine tissues and newly established cell lines covering different ontological stages and phenotypes applying novel bioinformatic pipelines. We will establish detailed knowledge on traits related to robustness, health and biological efficiency in cattle. Data, knowledge and protocols will be deposited in European biological archives, aiming to set up and maintain a knowledge hub and establish gold standards. Long-term availability of data and targeted dissemination and communication activities are guaranteed by EMBL-EBI, FAANG and EAAP. Our biology-driven genomic prediction tools will integrate biological knowledge on regulatory genomic variation into genomic selection schemes for local and global cattle populations. This improved knowledge will be useful for re-focussing cattle production, fully taking into account societal awareness, environmental and animal-welfare aspects and bio-efficiency.