HELZ is an ATP-dependent RNA helicase that functions as a key regulator of mRNA stability and translation. Its primary function involves promoting mRNA degradation through direct association with the CCR4-NOT deadenylase complex, which mediates deadenylation, decapping, and subsequent degradation of target mRNAs 1. Beyond mRNA decay, HELZ can independently repress translation in a manner dependent on both the CCR4-NOT complex and the helicase DDX6 1. At the cellular level, HELZ promotes cell proliferation, translation initiation, and ribosomal protein S6 (RPS6) phosphorylation 2. HELZ overexpression activates global protein translation, while its suppression reduces translational initiation and causes polysome disassembly, ultimately decreasing cell proliferation 2. Clinically, HELZ shows relevance in multiple disease contexts. Reduced HELZ expression correlates with improved FOLFOX chemotherapy response in metastatic colorectal cancer 3. Additionally, HELZ dysregulation appears significant in neuromyelitis optica spectrum disorder, where lnc-HELZ-7:1 was identified as a potential disease biomarker 4. HELZ mutations have been detected in papillary thyroid microcarcinoma associated with lymph node metastasis 5, and HELZ dysregulation may contribute to cardiomyocyte stress under hypoxic conditions 6.