Cysteine and glycine-rich protein 3 (CSRP3) (CSRP3)

Cysteine and glycine-rich protein 3 (CSRP3), also known as Muscle LIM protein (MLP), is a critical scaffold protein primarily expressed in cardiac and skeletal muscle (UniProt P50461). It contains two LIM domains that facilitate protein-protein interactions, allowing it to function as a dual-compartment protein: it maintains structural integrity at the sarcomeric Z-disc and shuttles to the nucleus to regulate myogenic transcription factors like MyoD (NCBI Gene ID: 1465). CSRP3 acts as a vital mechanosensor, translating mechanical stress into biochemical signals necessary for cardiac adaptation and remodeling (PubMed: 12479810). Mutations in the CSRP3 gene, such as the W4R variant, are strongly associated with various forms of cardiomyopathy, including dilated (DCM) and hypertrophic (HCM) phenotypes, often leading to heart failure (PubMed: 18247409). While no small-molecule drugs currently target CSRP3 directly, it is a primary candidate for gene therapy approaches aimed at restoring functional protein levels or correcting genetic defects (PubMed: 31558485). Therapeutic strategies focus on stabilizing its interaction with other cytoskeletal proteins like alpha-actinin and telethonin to preserve cardiac contractility.

Other names

Muscle LIM proteinMLPCRP3CMD1MCMH12LMO4Cardiac LIM protein

Gene replacement therapy to restore functional protein levels and stabilize the sarcomeric Z-disc mechanosensor complex (PubMed: 31558485)