Tcfl5, a transcription factor, is of great significance in multiple biological processes. It is involved in the regulation of gene expression, playing key roles in pathways related to spermatogenesis, cell differentiation, and tumor development [1,3,4,5,6]. Genetic models, especially KO mouse models, have been instrumental in deciphering its functions.

In spermatogenesis, Tcfl5-deficient mice generated by breeding TCFL5fl/fl with SOX2-Cre mice were sterile due to meiosis arrest and lack of spermatids. TCFL5 deficiency caused alterations during the pachytene/diplotene transition, leading to meiotic arrest in a diplotene-like stage. Tamoxifen-inducible TCFL5 knockout mice also showed abnormal spermatids elongation [3].

In DLBCL, knockdown of TCFL5 enhanced the sensitivity of cells to doxorubicin, as TCFL5 overexpression conferred drug-resistance via regulating GPX4 [2].

In esophageal cancer, circRNA TCFL5 promoted cancer progression by modulating M2 macrophage polarization via the miR-543-FMNL2 axis [5].

In colorectal cancer, different isoforms of TCFL5 had distinct effects on pro-tumoral properties and the regulation of pluripotency-related genes SOX2 and KLF4 [6].

In conclusion, Tcfl5 is essential for spermatogenesis, being indispensable for meiosis resolution and spermatids maturation. In disease areas, it is involved in drug-resistance in DLBCL, and the progression of esophageal and colorectal cancers. The study of Tcfl5 using KO mouse models has provided valuable insights into its functions in normal biological processes and disease conditions.