Despite being still not well studied, the understanding of the biological functions of SMYD5 has been steadily increasing in the past decade, including its role in toll-like receptor 4 (TLR4) signaling in macrophages [11], maintaining chromosome integrity during embryonic stem cell differentiation [12], a potential role in metastatic breast cancer dormancy [13], and a very recent study suggesting a role in sperm chromatin remodeling via direct binding to protamines [14]. This evidence concerns the gene TLR4 and breast cancer.