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Thyroid hormone-responsive protein (THRSP), also known as Spot 14 (S14), is a small acidic protein that functions as a critical regulator of lipid metabolism (UniProt P54111). It is primarily expressed in lipogenic tissues such as the liver, adipose tissue, and lactating mammary glands, where its expression is strongly induced by thyroid hormone (T3) and dietary carbohydrates (NCBI Gene 7069). THRSP acts as a transcriptional cofactor, modulating the expression of key enzymes involved in de novo lipogenesis, including fatty acid synthase (FASN) and ATP citrate lyase (ACLY) (PMID: 11440900). In clinical contexts, THRSP is often overexpressed in various malignancies, such as breast and liver cancer, where it supports the high metabolic demands of proliferating cells and is associated with poor prognosis (PMID: 25653145). Additionally, its role in hepatic fat accumulation makes it a potential therapeutic target for metabolic-associated steatotic liver disease (MASLD) (PMID: 22493091). While no small-molecule inhibitors are currently approved for clinical use, THRSP remains a subject of intense research for its potential to treat metabolic disorders and cancer by disrupting lipid synthesis pathways.
Transcriptional regulation of lipogenic enzymes
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