Gpr176, a member of the G-protein-coupled receptor superfamily, responds to external stimuli. It can couple to the G-protein subclass Gz (or Gx), participate in reducing cAMP production, and is involved in pathways like cAMP/PKA signaling [1,4]. Gpr176 has significant biological importance in processes such as circadian rhythm regulation in the suprachiasmatic nucleus (SCN) and is also associated with various diseases [3,4]. Genetic mouse models have been crucial for studying its functions.

In cancer, Gpr176-deficiency in genetic mouse models of colorectal cancer demonstrated its role in promoting cancer progression. Gpr176 activates the cAMP/PKA signaling pathway, modulates mitophagy via the GNAS-cAMP/PKA/BNIP3L axis, and promotes tumorigenesis and development of CRC [1]. In organ fibrosis, Gpr176-knockdown in mouse models showed its profibrotic role. In liver fibrosis models (carbon tetrachloride and common bile duct ligation), Gpr176-knockout mice developed less severe fibrosis, suggesting that Gpr176 in hepatic stellate cells is involved in fibrogenesis [2].

In conclusion, Gpr176 plays essential roles in regulating circadian rhythms and has significant impacts on cancer progression and organ fibrosis. Gene-knockout mouse models have been instrumental in uncovering these functions, providing insights into its roles in these disease areas.