CLK（Cdc2 样激酶）属于双特异性蛋白激酶家族，在通过SR 蛋白 (SRSF1-12) 的磷酸化，催化剪接体分子机制，以及调节非剪接蛋白的活性或表达。这些过程的失调与各种疾病有关，包括神经退行性疾病、杜氏肌营养不良症、炎症性疾病、病毒复制和癌症。因此，CLKs 被认为是潜在的治疗靶点，并且已经付出了巨大的努力来发现有效的 CLKs 抑制剂。特别是，旨在评估小分子 Lorecivivint 对膝关节骨性关节炎患者以及 Cirtuvivint 和 Silmitasertib 在不同晚期肿瘤中的活性的临床试验已被研究用于治疗用途。在这篇评论中，我们全面记录了 CLK 在各种人类疾病中的结构和生物学功能，并总结了相关抑制剂在治疗中的意义。我们的讨论重点介绍了最新的 CLK 研究，为各种人类疾病的临床治疗铺平了道路。

"点击查看英文标题和摘要"

The CLKs (Cdc2-like kinases) belong to the dual-specificity protein kinase family and play crucial roles in regulating transcript splicing via the phosphorylation of SR proteins (SRSF1–12), catalyzing spliceosome molecular machinery, and modulating the activities or expression of non-splicing proteins. The dysregulation of these processes is linked with various diseases, including neurodegenerative diseases, Duchenne muscular dystrophy, inflammatory diseases, viral replication, and cancer. Thus, CLKs have been considered as potential therapeutic targets, and significant efforts have been exerted to discover potent CLKs inhibitors. In particular, clinical trials aiming to assess the activities of the small molecules Lorecivivint on knee Osteoarthritis patients, and Cirtuvivint and Silmitasertib in different advanced tumors have been investigated for therapeutic usage. In this review, we comprehensively documented the structure and biological functions of CLKs in various human diseases and summarized the significance of related inhibitors in therapeutics. Our discussion highlights the most recent CLKs research, paving the way for the clinical treatment of various human diseases.