The Su(Var)3-9, Enhancer-of-zeste and Trithorax (SET) and Myeloid, Nervy, and DEAF-1 (MYND) domain-containing (SMYD) protein family consists of five members in humans and mice (i.e. SMYD1, SMYD2, SMYD3, SMYD4 and SMYD5), which are known or predicted to have methyltransferase activity on histone and non-histone substrates. The abundance of information concerning SMYD2 and SMYD3 is of note, whereas the other members of the SMYD family have not been so thoroughly studied CONCLUSION: Here we review the literature regarding SMYD proteins published in the last five years, including basic molecular biology mechanistic studies using in vitro systems and animal models, as well as human studies with a more translational or clinical approach.