The CDC-like kinase 1 (CLK1) dually phosphorylates serine and arginine rich proteins of the spliceosomal complex, which constitutes a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Specifically, CLK1 may mediate the release of specific proteins from nuclear storage sites. Expression of CLK1 may be very low due to a premature stop codon in the mRNA, which leads to nonsense-mediated mRNA decay. CLK1 activity is positively regulated by phosphorylation on either tyrosine residues or serine/ threonine residues, and is negatively regulated by steric constraints mediated by the N-terminal domain, and also by phosphorylation on a subset of serine/threonine residues within the catalytic domain.