Editorial on the Research TopicReceptor Biology and Cell Signaling in Diabetes Diabetes mellitus affects almost half a billion people around the globe, and nearly 25% of diabetic people eventually develop proteinuria, vascular dysfunction, and related kidney disease (Cooper and Warren, 2019). Organ fibrosis among diabetic patients is a leading cause of death worldwide. The cellular mechanisms of organ fibrosis and the origin of these fibroblasts are poorly understood (Srivastava et al.). Diabetes linked receptor dysfunctions result in defective central metabolism, disrupted cytoskeleton, and compromised organelle function, and it is likely associated with activation of cellular transdifferentiation processes causing fibrogenesis in organs such as the kidneys, heart, and blood vessels, ultimately leading to organ failure (Kang et al., 2015;Srivastava et al., 2018). Myofibroblasts metabolic shifts, cytokine and chemokine reprogramming, and autophagy defects are key examples of a critical phenomenon that influence the destruction of cellular structures, deposition of extracellular matrix, and fibrogenic pathways.Using contemporary cutting-edge technology, we have demonstrated the importance of glucocorticoid receptor (GR), fibroblast growth factor receptor 1, and sirtuin 3 mediated processes, which include suppression in myofibroblasts metabolic reprogramming, cytokine and chemokine reprogramming, inhibition in the levels of endothelial-to-mesenchymal transitions, and epithelial-to-mesenchymal processes in the diabetic kidneys (Figure 1) (Li et al., 2020a;Srivastava et al., 2021a;Srivastava et al., 2021c). Dipeptidyl transpeptidase-4 (DPP-4) and low-density lipoprotein receptor-related proteins 5 and 6 are key mesenchymal activators in diabetic tubules and endothelial cells. However, their interactions and their relation with myofibroblasts' metabolic reprogramming is a matter of ongoing research. Improved understanding of the pathogenesis of diabetes and associated kidney disease is urgently needed to catalyze the development of new therapeutics. Available therapies are neither tissue-nor cellspecific and are ineffective in reversing kidney fibrosis and diabetic complications.Recently, many renal protective agents that modulate the receptor physiology and improve cellular health and homeostasis, including sodium-glucose cotransporter inhibitors (SGLT-2), DPP-4 inhibitors, and N-seryl-acetyl-lysyl-proline, have been evaluated in preclinical settings and some in controlled clinical trials with promising outcomes (