在细胞中，信号转导很大程度上依赖于蛋白激酶的复杂调节，蛋白激酶为调节大多数信号通路提供了基本框架。激酶活性的失调与许多病理状况有关，特别是癌症。大多数激酶的可成药性质使它们成为药物开发过程中的焦点。然而，一个重大挑战仍然存在，因为近三分之一的人类激酶的作用和生物学功能在很大程度上仍然未知。在这个多样化的领域中，细胞周期蛋白依赖性激酶（CDK）作为一个有趣的分子亚群出现。在人类中，该激酶家族包含 21 个成员，参与多个关键的生物过程。值得注意的是，其中 13 个 CDK 属于尚未研究的激酶类别，并且迄今为止只有 5 个经过了广泛研究。这种知识差距强调了深入研究这些激酶的迫切需要，首先对较少探索的激酶进行全面回顾。在这里，我们将重点关注 CDK 的 PCTAIRE 亚家族，其中包括 CDK16、CDK17 和 CDK18，可以说是是研究最多的 CDK 成员之一。为了将 PCTAIRE 纳入人类病理生理学范围内，我们对现有文献进行了详尽的回顾并检查了可用的数据库。这种方法对这些 PCTAIRE 进行了清晰的描述，包括它们的表达模式、3D 配置、激活机制以及在正常组织和癌症中的潜在功能。我们建议这项工作提供了确定未来研究有希望的领域的可能性，这些领域将扩展从基础研究到潜在的临床和治疗应用。© 2024。作者。

In cells, signal transduction heavily relies on the intricate regulation of protein kinases, which provide the fundamental framework for modulating most signaling pathways. Dysregulation of kinase activity has been implicated in numerous pathological conditions, particularly in cancer. The druggable nature of most kinases positions them into a focal point during the process of drug development. However, a significant challenge persists, as the role and biological function of nearly one third of human kinases remains largely unknown.Within this diverse landscape, cyclin-dependent kinases (CDKs) emerge as an intriguing molecular subgroup. In human, this kinase family encompasses 21 members, involved in several key biological processes. Remarkably, 13 of these CDKs belong to the category of understudied kinases, and only 5 having undergone broad investigation to date. This knowledge gap underscores the pressing need to delve into the study of these kinases, starting with a comprehensive review of the less-explored ones.Here, we will focus on the PCTAIRE subfamily of CDKs, which includes CDK16, CDK17, and CDK18, arguably among the most understudied CDKs members. To contextualize PCTAIREs within the spectrum of human pathophysiology, we conducted an exhaustive review of the existing literature and examined available databases. This approach resulted in an articulate depiction of these PCTAIREs, encompassing their expression patterns, 3D configurations, mechanisms of activation, and potential functions in normal tissues and in cancer.We propose that this effort offers the possibility of identifying promising areas of future research that extend from basic research to potential clinical and therapeutic applications.© 2024. The Author(s).