FHL2 contains two highly conserved, tandemly arranged zinc finger domains, each binding a zinc atom through four conserved cysteines . These LIM domains serve as scaffolds for the assembly of multimeric protein complexes, facilitating interactions with other proteins and playing a crucial role in various cellular processes .
FHL2 is thought to function as a molecular transmitter linking various signaling pathways to transcriptional regulation . It negatively regulates the transcriptional repressor E4F1 and inhibits the transcriptional activity of FOXO1 by enhancing its interaction with SIRT1, leading to FOXO1 deacetylation . Additionally, FHL2 negatively regulates the calcineurin/NFAT signaling pathway in cardiomyocytes .
Mutations or dysregulation of the FHL2 gene have been associated with several diseases, including Familial Isolated Dilated Cardiomyopathy and Familial Hypertrophic Cardiomyopathy . The protein’s role in transcriptional regulation and signaling pathways makes it a potential target for therapeutic interventions in these conditions.