Gpr153, an orphan G-protein-coupled receptor, has its endogenous ligand yet to be clearly identified. It belongs to the Rhodopsin (class A) family of G protein-coupled receptors. Phylogenetic analysis suggests it may have an association with Adrenalin and Noradrenalin [2]. It is involved in various biological processes, and its expression in different tissues implies its importance in physiological and neuropathological mechanisms [1].

Gpr153 shows differential expression in various tissues. In heifers, it is expressed in anterior pituitary gonadotrophs in a stage-dependent manner, with lower expression during the early luteal phase compared to pre-ovulation or late luteal phases [3]. It colocalizes with the gonadotropin-releasing hormone receptor (GnRHR) in the plasma membrane of gonadotrophs, suggesting a role in regulating gonadotropin secretion [3,5]. In addition, in bovine anterior pituitary, its expression is differentially regulated before and after ovulation [6]. Also, in Wistar rats, its expression in the kidney is altered in diabetic nephropathy, indicating a possible involvement in this disease [4]. Moreover, it has been identified as a candidate gene in childhood-onset schizophrenia due to the presence of potentially pathogenic de novo variants [7].

In conclusion, Gpr153 plays important roles in reproductive regulation, as seen in heifers, and may be associated with diseases such as diabetic nephropathy and childhood-onset schizophrenia. Its differential expression in various tissues and disease conditions provides insights into its biological functions, and further research, potentially using gene knockout models in the future, could help to better understand its precise roles in these processes [3,4,6,7].