FHL3 (four and a half LIM domains 3) is a multifunctional LIM domain protein involved in transcriptional regulation, muscle development, and cellular signaling. As a transcriptional coactivator, FHL3 is recruited by SOX15 to FOXK1 promoters and can also function as a co-repressor, exemplified by its interaction with MZF-1 to suppress human high-affinity IgE receptor beta-chain gene expression 1. In muscle biology, FHL3 plays crucial roles in myogenesis and muscle organ development, with studies identifying it as a biomarker for muscle function improvement in myotonic dystrophy type 1 patients 2. The protein demonstrates diverse cellular effects, including inhibition of HepG2 cell growth while promoting ECV304 cell proliferation and increasing angiogenin gene expression 3. FHL3 participates in oncogenic pathways, particularly in hepatocellular carcinoma where it interacts with MAZ to promote KRAS transcription downstream of Hippo-YAP signaling 4. Additionally, FHL3 mediates cardiovascular protection by competitively binding to prevent ubiquitin-proteasome degradation of phosphorylated ERK1/2 and JNK, thereby inhibiting aortic valve calcification when disrupted by AMBP 5. The protein has also been identified as part of prognostic models in cancer and immune-related disorders 67.