Cysteine and glycine-rich protein 3 also known as cardiac LIM protein (CLP) or muscle LIM protein (MLP) is a protein that in humans is encoded by the CSRP3 gene. CSRP3 IS a small 194 amino acid protein, which is specifically expressed in skeletal and cardiac muscle. In rodents, CSRP3 has also been found to be expressed in neurons. Gene The CSRP3 gene was discovered in rat in 1994. In humans it was mapped to chromosome 11p15.1, where it spans a 20kb genomic region, organized in 6 exons. The full length transcript is 0.8kb, while a splice variant, originating from the alternative splicing of exons 3 and 4, was recently identified and designated MLP-b. Structure MLP contains two LIM domains (LIM1 and LIM2), each being surrounded by glycine-rich regions, and the two separated by more than 50 residues. LIM domains offer a remarkable ability for protein-protein interactions. Furthermore, MLP carries a nuclear localization signal at amino acid positions 64-69 MLP can be acetylated/deacetylated at the position 69 lysine residue (K69), by acetyltransferase (PCAF) and histone deacetylase 4 (HDAC4), respectively. In myocytes, MLP has the ability to oligomerize, forming dimers, trimers and tetramers, an attribute that impacts its interactions, localization and function. Protein interactions and localization MLP has been identified to bind to an increasing list of proteins, exhibiting variable subcellular localization and diverse functional properties. In particular, MLP interacts with proteins at the: Z-line, including telethonin (T-cap), alpha-actinin (ACTN), cofilin-2 (CFL2), calcineurin, HDAC4, MLP-b as well as to MLP itself; costameres, where it binds to zyxin, integrin linked kinase (ILK) and beta1-spectrin; intercalated discs, where it associates with the nebulin-related anchoring protein (NRAP); nucleus, where it binds to the transcription factors MyoD, myogenin and MRF4. M-line as well as plasma membrane localization of MLP has also been observed, however, the protein associations mediating this subcellular distribution are currently unknown. These diverse localization patterns and binding partners of MLP suggest a multitude of roles relating both to the striated myocyte cytoskeleton and the nucleus. The role of MLP in each of these two cellular compartments appears to be dynamic, with studies demonstrating nucleocytoplasmic shuttling, driven by its nuclear localization signal, over time and under different conditions. Function In the nucleus, MLP acts as a positive regulator of myogenesis and promotes myogenic differentiation. Overexpression of MLP enhances myotube differentiation, an effect attributed to the direct association of MLP with muscle specific transcription factors