钙 (Ca2+) 离子是无处不在且不可或缺的信号信使，几乎可以调节所有细胞功能。 Ca2 具有调节多种不同过程并引起细胞功能刺激特异性变化的独特能力，需要对 Ca2 信号进行感测和解码。 Ca2 感应蛋白，例如钙调蛋白，通过结合和修改多种效应蛋白的功能来解码 Ca2 信号。这些效应子包括 Ca2-钙调蛋白依赖性蛋白激酶激酶 2 (CaMKK2)，它是信号级联的核心成分，在重要的生理和病理生理过程（包括脑功能和癌症）中发挥关键作用。除了作为 Ca2 信号解码器的作用外，CaMKK2 还充当连接 Ca2 信号传导与能量代谢的重要连接点。通过激活代谢调节剂 AMP 激活蛋白激酶 (AMPK)，CaMKK2 将 Ca2 信号与细胞能量状态整合，从而使 Ca2 调节的细胞活动与能量可用性同步。在这里，我们回顾了 CaMKK2 的结构、调控和功能，并讨论了其作为神经系统疾病、代谢疾病和癌症治疗靶点的潜力。© 2024 作者。

Calcium (Ca2+) ions are ubiquitous and indispensable signaling messengers that regulate virtually every cell function. The unique ability of Ca2+ to regulate so many different processes yet cause stimulus specific changes in cell function requires sensing and decoding of Ca2+ signals. Ca2+-sensing proteins, such as calmodulin, decode Ca2+ signals by binding and modifying the function of a diverse range of effector proteins. These effectors include the Ca2+-calmodulin dependent protein kinase kinase-2 (CaMKK2) enzyme, which is the core component of a signaling cascade that plays a key role in important physiological and pathophysiological processes, including brain function and cancer. In addition to its role as a Ca2+ signal decoder, CaMKK2 also serves as an important junction point that connects Ca2+ signaling with energy metabolism. By activating the metabolic regulator AMP-activated protein kinase (AMPK), CaMKK2 integrates Ca2+ signals with cellular energy status, enabling the synchronization of cellular activities regulated by Ca2+ with energy availability. Here, we review the structure, regulation, and function of CaMKK2 and discuss its potential as a treatment target for neurological disorders, metabolic disease, and cancer.© 2024 The Author(s).