后生动物中的特定细胞状态是由基因表达程序的交响乐建立的，这需要转录因子和共激活剂之间复杂的协同相互作用。这些调节分子的失调与细胞状态转变有关，而细胞状态转变又导致多种疾病，包括发育障碍、代谢障碍，最重要的是癌症。十年前，大多数转录因子（疾病发展的关键推动因素）历来被视为“不可成药”；然而，在随后的几年里，大量文献证实它们可以通过转录共激活因子（它们在各种生理和分子过程中的同盟者）间接靶向。这些共激活因子与转录因子一起能够启动和调节正常生理功能所需的多种基因的转录，由此，这种相互作用的失调可能会促进组织特异性疾病表型。因此，有必要分析这些共同激活因素如何与其他因素协调调节特定的多边进程。拟议的综述试图详细阐述转录辅激活因子、它们在转录调控中的参与以及对病理生理条件的特定贡献。这篇综述还解决了一个尚未得到全面处理的问题，并希望将注意力集中在未来的研究上，这些研究将包括对患者友好的治疗策略，其中针对共激活剂的药物将具有增强的益处和减少的副作用。对当前可用的治疗干预措施和相关限制的更多见解最终将揭示众多旨在改善疾病和良好患者预后的先进治疗目标。© 2023。作者。

Specific cell states in metazoans are established by the symphony of gene expression programs that necessitate intricate synergic interactions between transcription factors and the co-activators. Deregulation of these regulatory molecules is associated with cell state transitions, which in turn is accountable for diverse maladies, including developmental disorders, metabolic disorders, and most significantly, cancer. A decade back most transcription factors, the key enablers of disease development, were historically viewed as 'undruggable'; however, in the intervening years, a wealth of literature validated that they can be targeted indirectly through transcriptional co-activators, their confederates in various physiological and molecular processes. These co-activators, along with transcription factors, have the ability to initiate and modulate transcription of diverse genes necessary for normal physiological functions, whereby, deregulation of such interactions may foster tissue-specific disease phenotype. Hence, it is essential to analyze how these co-activators modulate specific multilateral processes in coordination with other factors. The proposed review attempts to elaborate an in-depth account of the transcription co-activators, their involvement in transcription regulation, and context-specific contributions to pathophysiological conditions. This review also addresses an issue that has not been dealt with in a comprehensive manner and hopes to direct attention towards future research that will encompass patient-friendly therapeutic strategies, where drugs targeting co-activators will have enhanced benefits and reduced side effects. Additional insights into currently available therapeutic interventions and the associated constraints will eventually reveal multitudes of advanced therapeutic targets aiming for disease amelioration and good patient prognosis.© 2023. The Author(s).