MIF4GD (MIF4G domain containing) is a multifunctional protein that primarily regulates translation of histone mRNAs, which uniquely lack poly-A tails and instead contain 3' stem-loop structures. MIF4GD interacts with the histone RNA-binding protein SLBP and the eIF3 subunit INT6/EIF3E to facilitate efficient translation of these cell cycle-regulated mRNAs 1. The protein functions by participating in cap-dependent translational initiation and may help circularize histone mRNAs to enhance their translation. Beyond histone mRNA regulation, MIF4GD plays a critical role in cell cycle control by stabilizing the CDK inhibitor p27 through antagonizing CDK2-dependent phosphorylation at threonine 187 2. This stabilization occurs in both nucleus and cytoplasm, leading to reduced cell proliferation when MIF4GD is overexpressed. In hepatocellular carcinoma, MIF4GD expression is significantly reduced compared to normal tissues, and low expression correlates with poor patient prognosis 2. The protein also interacts with supervillin and may participate in cytokinesis regulation 3. These findings establish MIF4GD as an important regulator of both translational control and cell cycle progression, with potential therapeutic relevance in cancer treatment.