[7] Sam68 (the Src-Associated substrate in Mitosis of 68 kDa) is officially called KHDRBS1 (KH domain containing, RNA binding, signal transduction associated 1).

[8][9] Sam68 is predominantly nuclear and its major function in the nucleus is to regulate alternative splicing by recognizing RNA sequences neighboring the included/excluded exon(s).

Sam68 influences the alternative splicing of a number of genes central to processes such as neurogenesis and adipogenesis as well as diseases such as spinal muscular atrophy (SMA) and cancer.

[13] The role of Sam68 was further highlighted in spinal muscular atrophy (SMA), as Sam68 promotes the skipping of exon 7 leading to a non-functional SMN2 protein.

Direct evidence for the involvement of Sam68 in alternative splicing has been shown in promoting the inclusion of the variable exon 5 (v5) in CD44 correlating with cell migration potential.

[18] In addition, Sam68 in conjunction with hnRNPA1 influences the choice of the alternative 5' splice sites of Bcl-x regulating pro-survival and apoptotic pathways.

[26] Sam68-deficient mice were generated by targeted disruption of exons 4-5 of the sam68 gene, which encode the functional region of the KH domain.

[28] The Sam68-null mice exhibited motor coordination defects and fell from the rotating drum at lower speeds and prematurely compared to the wild-type controls.