Zfp36l1, a member of the RNA-binding zinc finger protein 36 (ZFP36) family, contains tandem CCCH-type zinc-finger motifs with RNA-binding property. It enhances the turnover of mRNAs containing AU-rich elements (AREs) in their 3'-untranslated regions (3'UTR), thus playing a crucial role in post-transcriptional regulation of numerous physiological processes, including cell transition, differentiation, and immune regulation [2,3].

In the context of diseases, liver-specific Zfp36l1-deficient (L1LKO) mice were protected from alcohol-induced hepatic steatosis, injury, and inflammation, likely by stabilizing Fgf21 mRNA [2]. In osteosarcoma, knockdown of Zfp36l1 promoted cell migration and lung metastasis by activating TGF-β signaling and increasing SDC4 expression, as Zfp36l1 regulated SDC4 mRNA decay through AREs in its 3'UTR [4]. In small cell lung cancers (SCLCs), loss-of-function screen showed Zfp36l1 is required for LSD1 inhibitor sensitivity. LSD1 represses Zfp36l1, and upon LSD1 inhibition, Zfp36l1 expression is restored, blocking SCLC neuroendocrine differentiation by destabilizing SOX2 and INSM1 mRNAs [1].

In conclusion, Zfp36l1 is a key regulator in post-transcriptional mRNA regulation. Studies using gene-knockout mouse models have revealed its significance in multiple disease areas, such as alcoholic liver disease, osteosarcoma metastasis, and SCLC neuroendocrine plasticity, providing insights into potential therapeutic targets for these diseases.