Abstract
•The principles of signal-based functioning of GRNs have been discussed in a wide range of contexts: from the simple bacteriophage λ lysis-lysogenic switch to the complex GRNs in humans comprising transcriptional regulatory networks, protein-protein interaction networks, and metabolic networks. The ultimate phenotypes of complex organisms result from functional GRNs, where the gene expression pattern is fundamentally regulated by the interactions of gene and environmental factors.•The first hint that multiple genes may work together came from the discovery of the phenomenon, Epistasis, the nonallelic interactions in gene functions. As an example, we have presented how the phenomenon of Epistasis is involved in the manifestation of AD. Understanding the GRNs involved in AD pathogenesis could be useful for designing effective therapeutics.•siRNA- and shRNA-mediated knockdown of genes followed by transcriptome analysis are the major tools for elucidating the GRN.•One of the most well-studied GRNs, with physiological and pathophysiological contexts, is the tumor suppressor and master cell cycle regulatory network, Rb pathway. The multifunctional Rb pathway seems to be involved in a wide range of physiological processes, from cell proliferation to cellular plasticity, through its interactions with more than 300 proteins and regulating the expression of a large number of genes, including epigenetic modulators. Understanding of RB1 pathway is guiding the discovery of targeted cancer therapeutics. A few of these have already received FDA approval to be used in the clinics.•Reversal of the epigenetic landscape is no longer a dream or fiction. It is proven today that the ectopic expression of 3–4 TFs can induce pluripotency in any differentiated cells. It is also possible to push the cells from one lineage to another by using these TFs. Most interestingly, this kind of cell reprogramming is also possible by a set of small molecule compounds targeting epigenetic enzymes, kinases, etc. These discoveries have created tremendous potential in drug discovery and regenerative medicines.