Four and a half LIM domains protein 2 also known as FHL-2 is a protein that in humans is encoded by the FHL2 gene. LIM proteins contain a highly conserved double zinc finger motif called the LIM domain. Function FHL-2 is thought to have a role in the assembly of extracellular membranes and may function as a link between presenilin-2 and an intracellular signaling pathway. Family The Four-and-a-half LIM (FHL)-only protein subfamily is one of the members of the LIM-only protein family. Protein members within the group might be originated from a common ancestor and share a high degree of similarity in their amino acid sequence. These proteins are defined by the presence of the four and a half cysteine-rich LIM homeodomain with the half-domain always located in the N-terminal. The name LIM was derived from the first letter of the transcription factors LIN-11, ISL-1 and MEC-3, from which the domain was originally characterized. No direct interactions between LIM domain and DNA have been reported. Instead, extensive evidence points towards the functional role of FHL2 in supporting protein-protein interactions of LIM-containing proteins and its binding partners. Thus far, five members have been categorized into the FHL subfamily, which are FHL1, FHL2, FHL3, FHL4 and activator of CREM in testis (ACT) in human. FHL1, FHL2 and FHL3 are predominantly expressed in muscle, while FHL4 and FHL5 are expressed exclusively in testis. Gene FHL2 is the best studied member within the subfamily. The protein is encoded by the fhl2 gene being mapped in the region of human chromosome 2q12-q14. Two alternative promoters, 1a and 1b, as well as 5 transcript variants of fhl2 have been reported. Tissue distribution FHL2 exhibits diverse expression patterns in a cell/tissue-specific manner, which has been found in liver, kidney, lung, ovary, pancreas, prostate, stomach, colon, cortex, and in particular, the heart. However, its expression in some immune-related tissues like the spleen, thymus and blood leukocytes has not been documented. Intriguingly, the FHL2 expression and function varies significantly between different types of cancer. Such discrepancies are most likely due to the existence of the wide variety of transcription factors governing FHL2 expression. Regulation of expression Different transcription factors that have been reported responsible for the regulation of fhl2 expression include the well-known tumor suppressor protein p53, serum response factor (SRF), specificity protein 1 (Sp1). the pleiotropic factor IL-1β, MEF-2, and activator protein-1 (AP-1). Apart from being regulated by