Gpr149, an orphan G protein-coupled receptor, has been implicated in multiple biological processes. Its functions span from energy homeostasis regulation to involvement in myelination, and it may also play roles in neuronal development-related pathways and cancer-associated processes [1,2,3,4]. It could potentially be associated with pathways like MAPK/ERK based on current research [2]. Genetic models, especially KO mouse models, are valuable for studying its functions in vivo.

In male mice, Gpr149-deficient mice partially resist weight gain on a high-fat diet and show greater insulin sensitivity, indicating its role in energy homeostasis [1]. In the context of myelination, Gpr149 deficiency promotes oligodendrocyte precursor cell (OPC) to oligodendrocyte (OL) differentiation, leading to earlier myelin development and enhanced myelin regeneration in a cuprizone-induced demyelination model, suggesting it negatively regulates myelination and remyelination [2]. Deletion of Gpr149 in mice leads to increased fertility, with enhanced ovulation and increased oocyte Gdf9 mRNA levels, along with increased levels of FSH receptor and cyclin D2 mRNA levels in granulosa cells [5].

In conclusion, Gpr149 is involved in crucial biological functions such as energy balance, myelination, and female fertility. The gene knockout mouse models have significantly contributed to understanding its roles in these areas, providing insights into potential therapeutic targets for conditions like diet-induced obesity, demyelinating diseases, and infertility [1,2,5].