Fhl2, also known as LIM protein FHL2, is a member of the LIM-only family. As a multifunctional adaptor and scaffolding protein, it can interact with various proteins such as cell surface receptors, cytosolic adaptors, kinases, and nuclear transcription factors. It is involved in numerous functional activities including gene expression regulation, cell growth, signal transduction, epithelial-mesenchymal transition, cell proliferation, apoptosis, adhesion, migration, and structural stability [1,2,3]. It participates in pathways like EGF/EGFR/YAP, Hippo/YAP, and is related to many physiological and pathological events [4]. Gene knockout models have been crucial in studying its functions.

Fhl2 knockout (KO) mouse models have revealed its diverse roles. In female fertility, Fhl2 deficiency impairs follicular development and reduces litter size and offspring number by attenuating EGF/EGFR/YAP signaling in ovarian granulosa cells [4]. In arterial medial calcification related to chronic kidney disease, FHL2 is up-regulated in arterial vascular smooth muscle cells (VSMCs) of CKD subjects. Inhibition of FHL2 expression in VSMCs can prevent their transdifferentiation into an osteogenic phenotype and mitigate aortic calcification in uremic animals without harming the skeletal system [5].

In conclusion, Fhl2 is a key regulator in multiple biological processes. Model-based research, especially Fhl2 KO mouse models, has shown its significance in female fertility and arterial medial calcification in chronic kidney disease. These findings help us understand the underlying mechanisms and potentially develop new therapeutic strategies for related diseases.