Cdc2-like kinase family (CLK family)

Cdc2-like kinases (CLKs) are a subfamily of dual-specificity protein kinases within the CMGC group, consisting of four human members: CLK1, CLK2, CLK3, and CLK4. CLKs phosphorylate serine, threonine, and tyrosine residues, mainly targeting SR proteins (SRSF1–12) crucial for spliceosome assembly and pre-mRNA splicing. Through these actions, CLKs regulate gene expression at the RNA processing level and thereby influence protein synthesis. Abnormal CLK function or expression is linked to several diseases, including cancer and neurodegeneration, making them attractive therapeutic targets. Modulation of CLK activity—particularly inhibition—can alter aberrant splicing events that contribute to pathogenesis. Several small-molecule CLK inhibitors are in clinical development, highlighting this kinase family's emerging therapeutic potential

Other names

CDC-like kinase familyCdc2-like kinasesCLK kinasesCLKsLAMMER kinases (context-dependent; less common)Dual specificity protein kinases CLK1, CLK2, CLK3, CLK4 (individual members)

Inhibition of kinase activity (block phosphorylation of SR proteins); Modulation of alternative splicing pathways; Downregulation of disease-associated mis-splicing or aberrant splicing events