Zfp36l2, a member of the tristetraprolin family of CCCH zinc finger proteins, is an RNA-binding protein. It plays a pivotal role in post-transcriptional modifications by stimulating the degradation of target mRNAs [1,2,3]. It is involved in multiple biological pathways and is of great biological importance, with genetic models like KO/CKO mouse models being valuable for its study.

In thyroid-specific Zfp36l2-/-female mice, hypothyroidism occurred due to dyshormonogenesis, with decreased levels of thyroid-specific transcripts and proteins, increased apoptosis, and an altered response to TSH stimulation. Mechanistically, Notch1 was confirmed as a target of ZFP36L2 in the thyroid [1]. In osteosarcoma, ZFP36L2 was associated with metastasis in sarcoma, and can serve as a biomarker in IL1β + osteosarcoma [2]. Genetic inhibition of Zfp36l2 in leukemia cells restored the mRNA stability of key myeloid maturation genes and triggered myeloid differentiation [3]. In T-lineage acute lymphoblastic leukemia, ZFP36L2 was identified as a putative driver gene [4]. In muscle, the lncRNA ZFP36L2-AS, which is specifically enriched in skeletal muscle, was found to regulate muscle development and metabolism [5]. In lower-grade glioma, high ZFP36L2 expression predicted poor clinical outcomes and was involved in immune-response-related pathways [6]. In asthma, ZFP36L2 was dysregulated in the airway epithelium, and restoring its level in primary bronchial epithelial cells from severe asthma patients decreased the mRNA expression of IL6, IL8, and CSF2 [7]. In mice, cardiac-specific Zfp36l2 deletion led to rapid cardiac dysfunction after delivery, as ZFP36L2 negatively regulated mTORc1 activation during pregnancy through a P53-dependent pathway [8]. A homozygous variant in ZFP36L2 caused female infertility due to oocyte maturation defect, as it decreased the protein levels of ZFP36L2 in oocytes and might lead to the loss of its function to degrade maternal mRNAs [9]. T cell-specific deletion of both Zfp36l1 and Zfp36l2 in mice rendered them resistant to experimental autoimmune encephalomyelitits due to failed priming of antigen-specific CD4+ T cells, and ZFP36L1 and ZFP36L2 double-deficient CD4+ T cells had poor proliferation during in vitro T helper cell polarization [10].

In conclusion, Zfp36l2 is crucial in multiple biological processes such as thyroid function, muscle development, oocyte maturation, and T-cell regulation. Through KO/CKO mouse models, its roles in diseases like hypothyroidism, osteosarcoma, leukemia, LGG, asthma, peripartum cardiomyopathy, and female infertility have been revealed. These studies contribute to understanding the molecular mechanisms underlying these biological processes and diseases, providing potential targets for treatment.