Gpr107, a type III integral membrane protein, was initially predicted as a member of the G-protein-coupled receptor family. It localizes to the trans-Golgi network and is essential for retrograde transport [1]. Gpr107 is also involved in receptor-mediated endocytosis and recycling, and might be responsible for returning receptors to the plasma membrane from endocytic compartments [4].

Deletion of Gpr107 in mice leads to an embryonic lethal phenotype, with reduced cubilin transcript abundance and decreased representation of genes in the cubilin-megalin endocytic receptor complex [4]. Gpr107-null fibroblast cells show reduced transferrin internalization, decreased uptake of low-density lipoprotein (LDL) receptor-related protein-1 (LRP1) cargo and resistance to toxins, indicating its role in these cellular processes [4]. In pancreatic α-cells, compromising Gpr107 results in failure of neuronostatin (NST) to increase PKA phosphorylation and proglucagon mRNA levels, suggesting Gpr107 is involved in NST-mediated signaling in these cells [2].

In summary, Gpr107 plays crucial roles in intracellular vesicular transport, receptor-mediated endocytosis and recycling, and specific signaling pathways in pancreatic cells. Gene-knockout mouse models have revealed its importance in these biological processes, and its potential association with diseases such as prostate cancer, where Gpr107 is overexpressed and associated with key clinical parameters [3].