Four and a half LIM domains protein 3 (FHL3)

Four and a half LIM domains protein 3 (FHL3) is a member of the LIM-only protein family, characterized structurally by four complete LIM domains plus a fifth N-terminal half LIM domain, each functioning as zinc finger motifs for protein-protein interactions. FHL3 acts primarily as an adaptor or scaffold, modulating the assembly of signaling complexes, regulating transcription (acting both as co-activator and co-repressor), and influencing cytoskeletal organization, especially in skeletal muscle where its expression is strongest and often restricted. Through these functions, FHL3 plays important roles in myogenesis, muscle regeneration, and diverse cellular signaling pathways (including TGFβ/SMAD, AKT, GSK3β). In cancer biology, FHL3 can act either as a tumor suppressor or promoter depending on tissue type and tumor context, with evidence of roles in hepatocellular carcinoma, breast cancer, gastric cancer, and glioma among others. FHL3 does not have known direct small molecule or biologic modulators, but its expression or function may serve as a biomarker for several cancer types or muscle diseases.

Other names

FHL3SLIM2FHL-3SLIM-2Skeletal muscle LIM-protein 2LIM-only protein FHL3

Not directly targeted by approved drugs; FHL3 modulates disease processes through protein-protein interactions and transcriptional scaffolding.