Beyond olfaction: New insights into human odorant binding proteins

Until today, the exact function of mammalian odorant binding proteins (OBPs) remains a topic of debate. Although their main established function lacks direct evidence in human olfaction, OBPs are traditionally believed to act as odorant transporters in the olfactory sense. Now, available RNA-seq and proteomics data identified the expression of the two known human OBPs (hOBP2A and hOBP2B) in both male and female reproductive tissues. Therefore, we hypothesize that OBPs may possess functions that go beyond the olfactory sense, potentially as hormone transporters. Such a function could further link them to the tumorigenesis and cancer progression of hormone-dependent cancer types including ovarian, breast, prostate, and uterine cancer. In this structured review, we use available data to explore the effects of genetic alterations such as somatic copy number aberrations and single nucleotide variants on OBP function and their corresponding gene expression profiles. Our computational analyses suggest that somatic copy number aberrations in OBPs are associated with large changes in gene expression in reproductive cancers while point mutations have little to no effect. Additionally, the structural characteristics of OBPs, together with other lipocalin family members, allow us to explore putative functions within the context of cancer biology. Our overview consolidates current knowledge on putative human OBP functions, their expression patterns, and structural features. Finally, it provides an overview of applications, highlighting emerging hypotheses and future research directions within olfactory and non-olfactory roles.