p21-Activated kinase 4 (PAK4), a member of the PAK family, regulates a wide range of cellular functions, including cell adhesion, migration, proliferation, and survival. Dysregulation of its expression and activity thus contributes to the development of diverse pathological conditions. PAK4 plays a pivotal role in cancer progression by accelerating the epithelial–mesenchymal transition, invasion, and metastasis. Therefore, PAK4 is regarded as an attractive therapeutic target in diverse types of cancers, prompting the development of PAK4-specific inhibitors as anticancer drugs; however, these drugs have not yet been successful. PAK4 is essential for embryonic brain development and has a neuroprotective function. A long list of PAK4 effectors has been reported. Recently, the transcription factor CREB has emerged as a novel effector of PAK4. This finding has broad implications for the role of PAK4 in health and disease because CREB-mediated transcriptional reprogramming involves a wide range of genes. In this article, we review the PAK4 signaling pathways involved in prostate cancer, Parkinson’s disease, and melanogenesis, focusing in particular on the PAK4-CREB axis.

p21 活化激酶 4 (PAK4) 是 PAK 家族的成员，可调节多种细胞功能，包括细胞粘附、迁移、增殖和存活。因此，其表达和活性的失调有助于各种病理状况的发展。PAK4通过加速上皮-间质转化、侵袭和转移在癌症进展中起关键作用。因此，PAK4 被认为是多种癌症的有吸引力的治疗靶点，促进了 PAK4 特异性抑制剂作为抗癌药物的开发；然而，这些药物还没有成功。PAK4 对胚胎大脑发育至关重要，并具有神经保护功能。已经报道了一长串 PAK4 效应器。最近，转录因子 CREB ​​已成为 PAK4 的一种新型效应物。这一发现对 PAK4 在健康和疾病中的作用具有广泛的意义，因为 CREB ​​介导的转录重编程涉及广泛的基因。在本文中，我们回顾了涉及前列腺癌、帕金森病和黑色素生成的 PAK4 信号通路，特别关注 PAK4-CREB ​​轴。