The „KRAB-ZNF“ initiative is driven by recent observations that KRAB-ZNF genes, an evolutionarily conserved gene family of more than 350 transcriptional repressors encoded in the human genome, are predominantly expressed in testis and fetal brain. To elucidate functions of KRAB ZNF genes in evolution and diseases, experts in KRAB ZNF gene biology (B1/P1), proteomics (B1/P2), systems biology and aging (B2/P3), interspecies brain life histories (B3/P4), primate socioecology (B3/P5), human pathology (B3/P6) and in any aspect of computational biology (B4/P7-B6/P11) have established a well-coordinated interdisciplinary exchange program between German (B1,B2/P1-P3), Swiss (B3,P4-P6) and Chinese (B4/P7-B6/P11) institutions. Bioinformatic expertise encompasses network analysis (B4/P7 and B6/P10), molecular structure modeling (B5/P9), database design (B4/P8), and deep sequencing bioinformatics (B6/P11). Workpackages with defined topics are focused on the toponome analysis of KRAB ZNF protein expression (WP1), studying KRAB-ZNF interactions with TRIM28 (WP2), relating KRAB-ZNF gene functions to longevity (WP3), comparing brain sizes, fertility, cognitive behaviours and other aspects of life histories from birds to mammals (WP4), correlating SNPs of brain-related genes with social behaviour of e.g. primates (WP5), and on studying KRAB ZNF protein and related target proteins thereof in human pathology (WP6). The experimental data (B1/P1-B3/P6) will be analyzed in conjunction with experts in bioinformatics (B4/P7-B6/P11), compared to existing world-wide-knowledge (WP7), upon perturbation by small molecules (WP8), modeled upon protein interaction data (WP9), assembled in comprehensive databases (WP10), and finally analyzed phylogenomically (WP11). Within the requested funding period of 48 months, the “KRAB-ZNF” initiative is expected to achieve major contributions in elucidating KRAB ZNF gene functions in primate evolution, ontogenesis, neural development, longevity and disease.