FRG2 (FSHD region gene 2) encodes a long noncoding RNA (lncRNA) that plays a crucial role in ribosomal regulation and protein synthesis in skeletal muscle cells. FRG2A localizes to the nucleolus and associates with repetitive DNA at ribosomal DNA loci and centromeres, where elevated expression alters three-dimensional heterochromatin architecture and reduces rRNA transcription and translation rates 1. This results in decreased synthesis of skeletal muscle proteins, linking FRG2 dysfunction to muscle wasting in facioscapulohumeral muscular dystrophy (FSHD) 1. The gene is transcriptionally upregulated specifically in differentiating FSHD myoblasts through direct activation by the DUX4 transcription factor, which binds to FRG2 promoter sequences 2. FRG2 transcripts are chr4-associated and undergo posttranscriptional stabilization in response to DNA damage, with stabilization levels inversely correlated with D4Z4 repeat number 3. Beyond FSHD, FRG2 functions as a cancer stemness negative regulator in triple negative breast cancer, where its deletion promotes paclitaxel resistance and tumor metastasis, while increased expression sensitizes tumors to treatment 4. The protein shows nuclear localization and its overexpression causes morphological changes in cells 5.