The family of IGFBPs has been developed by the duplication of genes and genomes and contributes to genetic and functional diversity. Due to the different protein domains present in the molecule, IGFBPs can be seen as mediators of tissue-specific IGF-functions. However, IGFBPs also have IGF-independent functions both inside and outside the cell. These diverse genetic, molecular and functional aspects of IGFBPs are discussed within this Research Topic. Accumulating data provide evidence for the regulation of IGFBP-functions by proteases, which may acutely regulate bioactivity of the IGFs. However, during proteolytic degradation IGFBP-fragments with novel functions can also be formed and are located both intra- and extracellularly. Distinct IGFBP-fragments can even be found in the perinuclear compartment or within the nucleus, where they can impact on gene expression. Several contributions presented in the current Research Topic particularly stress the relevance of structural aspects in IGFBP research. The current lack of comprehensive structural information is dramatically limiting the biomarker potential of particular IGFBPs. Finally, the Research Topic also provides novel functions of the IGFBP family from model organisms, farm animals and humans. Thereby, the biomarker potential not only relates to normal and malignant growth but also to metabolism and animal welfare. One important aim of the Research Topic is to encourage next generation IGFBP research reflecting subject-individual, conditional, and hormonal parameters but also structural aspects of the IGFBPs.