CLK4 (CDC-like kinase 4) is a dual-specificity kinase that phosphorylates both serine/threonine and tyrosine residues on spliceosomal proteins, particularly serine- and arginine-rich (SR) proteins including SRSF1, SRSF3, SRSF4, and SRSF6 1. The kinase regulates alternative splicing of key genes including MAPT/TAU and tissue factor (F3) pre-mRNA, enabling SR proteins to control RNA splicing processes 1. CLK4 is expressed across all human tissues with prominent expression in liver, kidney, brain, and heart 1. Beyond splicing, CLK4 functions in metabolic regulation and redox homeostasis; low CLK4 expression promotes purine synthesis and affects NADPH/NADP+ ratios through MITF-dependent mechanisms 2. CLK4 exhibits redox sensitivity, with methionine oxidation impairing kinase activity 2. Clinically, CLK4 variants associate with chr5 and sleep-related traits 3. Elevated CLK4 expression correlates with poor survival in triple-negative breast cancer, where it promotes epithelial-mesenchymal transition and metastasis via TGF-β pathway activation 4. In pancreatic cancer, CLK4 inhibition suppresses cell growth, induces G2/M arrest, and modulates alternative splicing of cancer-promoting genes 5. These findings establish CLK4 as a therapeutic target in cancer and potentially sleep disorders 6.