Esr1, or Estrogen Receptor 1, is a key gene encoding the estrogen receptor-alpha protein. It plays a crucial role in estrogen-mediated signaling pathways, which are involved in various biological processes, especially those related to reproductive and endocrine functions. Alterations in Esr1 can have significant implications for human health, making it an important subject for in-vivo functional studies using gene knockout models [6].

In breast cancer, Esr1 mutations are a common mechanism of hormonal therapy resistance. They can pre-exist in primary tumors and be enriched during metastasis. These mutations express a unique transcriptional profile that promotes tumor progression. Detection of Esr1 mutations in circulating tumor DNA (ctDNA) via liquid biopsy, using methods like digital droplet PCR (ddPCR) or next-generation sequencing (NGS), can help predict treatment outcome and tumor progression. Clinically, patients with Esr1-mutant tumors benefit from treatments like fulvestrant and CDK4/6-targeted therapies [1,2,3,5,6].

In adolescent idiopathic scoliosis (AIS), ESR1 expression declines in muscle stem/progenitor cells at the concave side of AIS patients. Disrupted ESR1 signaling leads to differentiation defects, and the imbalance of ESR1 signaling in para-spinal muscles can induce scoliosis in mice [4].

In conclusion, Esr1 is essential for normal physiological functions through its role in estrogen-mediated signaling. Gene knockout or other loss-of-function models have revealed its significance in diseases such as breast cancer and adolescent idiopathic scoliosis. Understanding Esr1 functions and its mutations can potentially guide more effective treatment strategies for these diseases.