ZFP36L1 is a zinc-finger RNA-binding protein that regulates gene expression post-transcriptionally by binding to AU-rich elements (AREs) in the 3' untranslated regions of target mRNAs and promoting their deadenylation and decay. The protein recruits the CCR4-NOT deadenylase complex to facilitate mRNA destabilization, thereby attenuating protein synthesis of specific targets. ZFP36L1 functions in diverse physiological contexts: it negatively regulates erythroid differentiation through STAT5B mRNA decay, promotes monocyte/macrophage differentiation via CDK6 mRNA degradation, and maintains quiescence in developing B lymphocytes by degrading cell-cycle regulators. Beyond its cytoplasmic role in mRNA decay, ZFP36L1 also modulates nuclear mRNA 3'-end processing and regulates stress granule formation. In disease contexts, ZFP36L1 dysregulation associates with multiple malignancies and inflammatory conditions. In diffuse large B-cell lymphoma, ZFP36L1 mutations are part of the ST2-like genetic subtype, which shows favorable outcomes in germinal center B-cell lymphomas 1. In small cell lung cancer, LSD1 inhibitor-induced restoration of ZFP36L1 expression blocks neuroendocrine differentiation by destabilizing SOX2 and INSM1 mRNAs 2. ZFP36L1 expression is significantly reduced in severe asthma airways, where restoration in primary bronchial epithelial cells decreases pro-inflammatory cytokine transcripts 3. In osteosarcoma, low ZFP36L1 promotes lung metastasis through SDC4-TGF-β signaling activation, suggesting that TGF-β receptor inhibitors and MAPKAPK2 inhibitors may enhance metastasis suppression 4. ZFP36L1 also regulates mTOR-controlled senescence phenotypes by controlling MAPKAPK2 translation-dependent phosphorylation 5.