Grk6, short for G protein-coupled receptor kinase 6, is a key kinase within the GPCR-related family. It is involved in regulating G protein-coupled receptor signaling and participates in multiple important biological pathways, influencing various physiological and pathological processes [1-10].

In lung adenocarcinoma, GRK6 depletion in alveolar epithelial type II cells, achieved by RNA interference, induces HIF1α levels and activity, potentially via regulation of VHL levels, indicating its role in cancer-related hypoxia pathways [1]. In platelets, GRK6-/-mice show increased platelet activation and larger hemostatic thrombi during early thrombus formation, revealing its role in regulating the hemostatic response through PAR-and P2Y12-mediated effects [2]. GRK6-/-mice also exhibit lymphocytopenia and loss of hematopoietic stem cell and progenitor populations, suggesting its importance in hematopoiesis and regulation of reactive oxygen species signaling [3]. In pulmonary arterial hypertension models, knockout of GRK6 exacerbates the condition, while overexpression alleviates it by attenuating hypoxia-induced pulmonary arterial smooth muscle cell proliferation and STAT3 phosphorylation [4].

In conclusion, GRK6 plays diverse and crucial roles in multiple biological processes and disease conditions. Gene-knockout mouse models, such as GRK6-/-mice, have been instrumental in revealing these functions, especially in areas like cancer, hemostasis, hematopoiesis, and pulmonary arterial hypertension, providing valuable insights into potential therapeutic strategies for related diseases.