Mammalian cell pre-mRNA splicing is mediated by the spliceosome, a multi-component complex that contains two types of splicing factors: small nuclear ribonucleoprotein particles (snRNPs) and non-snRNP factors. Interactions between snRNPs and pre-mRNA ensures proper establishment of a catalytic core for the splicing reaction. However, these interactions are mediated by the non-snRNP factors. The super family of Arg/Ser-rich (RS) domain containing splicing factors are well known non-snRNPs. All of these proteins share a similar structure consisting of an N-terminal RNA recognition motif and a C-terminal RS domain. However, different SR factors have distinct specificities and function is regulated by their level of expression and by reversible phosphorylation. Two families of kinases phosphorylate SR domain-containing proteins: SR protein-specific kinases (SRPK1 and 2) and Clk/Sty. SRPL1 is specific for SR domain-containing splicing factors because it recognizes only Arg and phosphorylates only Ser. SRPK1 is expressed predominately in the pancreas, domain-containing splicing factors because it recognizes only Arg and phosphorylates only Ser. SRPK1 is expressed predominately in the pancreas, whereas SRPK2 is highly expressed in brain. SRPKs affect splice-site selection and are thought to affect alternative splicing.