FRG1, short for FSHD region gene 1, is the primary candidate gene for Fascioscapulohumeral Muscular Dystrophy. It is involved in multiple biological processes, such as muscle development, vasculogenesis, angiogenesis, and tumorigenesis, and is associated with pathways like mRNA surveillance, RNA transport, and spliceosome machinery [1,2,3,5,6]. Genetic models, like those in Xenopus laevis and mice, have been crucial for studying its functions [7,8].

In vertebrate embryonic development, frg1 in Xenopus laevis is expressed in and essential for tadpole musculature development. Disrupting normal FRG1 levels, either through morpholino injection or over-expression, leads to abnormal muscle formation, suggesting its critical role in proper muscle development [7]. In mice, over-expression of FRG1 in myoblasts isolated from thigh muscle results in delayed proliferation, which may contribute to the pathology of mice over-expressing FRG1 and potentially play a part in FSHD [8]. In cancer research, reduced FRG1 expression promotes angiogenesis via activation of the FGF2-mediated ERK/AKT pathway in breast cancer, and affects migration and invasion in AR-negative prostate cancer cells through known MMPs and cytokines, mainly via p38 MAPK activation [2,4]. Also, FRG1 might be a transcriptional regulator of nonsense-mediated mRNA decay (NMD) genes, and it plays a role in DNA repair in breast cancer [1,3].

In summary, FRG1 is essential for muscle development and has a significant impact on angiogenesis, tumorigenesis, and mRNA surveillance. Mouse models, especially those with over-expression or reduced expression of FRG1, have been instrumental in revealing its role in FSHD and cancer-related processes, contributing to our understanding of these disease mechanisms.