While some studies have linked SMYD3 overexpression in cancer cells to transcriptional regulation via its activity on histone 3 lysine 4 (H3K4) methylation, biochemical evidence indicates that H3K4 is not a direct target for methylation by SMYD3 (37) and SMYD3 is predominantly cytoplasmic in many cell types (40). Here, SMYD3 is linked to cancer.