Grk6, short for G protein-coupled receptor kinase 6, is a kinase of GPCRs. It is expressed in various tissues and is involved in regulating multiple signaling pathways. GRK6 plays a crucial role in many biological processes, such as inflammation regulation, hemostasis, hematopoiesis, and insulin processing. Genetic models, especially KO mouse models, have been valuable in studying its functions [1-8].

GRK6 -/- mice exhibit larger hemostatic thrombi during early thrombus formation, increased platelet activation in an agonist-selective manner, and enhanced Ca2+ mobilization, Akt activation, and granule secretion, indicating its role in regulating the hemostatic response [3]. In addition, GRK6 knockout mice show lymphocytopenia, loss of hematopoietic stem cell and multiple progenitor populations, and compromised lymphoid differentiation due to impaired HSC self-renewal [4]. In lung adenocarcinoma, depletion of GRK6 induces HIF1α levels and activity, and in Kupffer cells, LPS-induced inflammation is affected by GRK6 palmitoylation and its membrane translocation [1,2].

In conclusion, Grk6 is essential in regulating hemostasis, hematopoiesis, and inflammation-related processes. Studies using KO mouse models have revealed its significance in diseases like lung adenocarcinoma, suggesting that targeting Grk6-related pathways may provide new therapeutic strategies for these diseases.