Mutations in the gene BEST1 are causally associated with as many as five clinically distinct retinal degenerative diseases, which are collectively referred to as the “bestrophinopathies”. These five associated diseases are: Best vitelliform macular dystrophy, autosomal recessive bestrophinopathy, adult-onset vitelliform macular dystrophy, autosomal dominant vitreoretinochoroidopathy, and retinitis pigmentosa. The most common of these is Best vitelliform macular dystrophy. Bestrophin 1 (Best1), the protein encoded by the gene BEST1, has been the subject of a great deal of research since it was first identified nearly two decades ago. Today we know that Best1 functions as both a pentameric anion channel and a regulator of intracellular Ca²⁺ signaling. Best1 is an integral membrane protein which, within the eye, is uniquely expressed in the retinal pigment epithelium where it predominantly localizes to the basolateral plasma membrane. Within the brain, Best1 expression has been documented in both glial cells and astrocytes where it functions in both tonic GABA release and glutamate transport. The crystal structure of Best1 has revealed critical information about how Best1 functions as an ion channel and how Ca²⁺ regulates that function. Studies using animal models have led to critical insights into the physiological roles of Best1 and advances in stem cell technology have allowed for the development of patient-derived, “disease in a dish” models. In this article we review our knowledge of Best1 and discuss prospects for near-term clinical trials to test therapies for the bestrophinopathies, a currently incurable and untreatable set of diseases.

BEST1基因的突变与多达五种临床上不同的视网膜变性疾病有因果关系，这些疾病统称为“雌激素病”。这五种相关疾病分别是：最佳黄斑性黄斑营养不良，常染色体隐性性甲虫病，成年发病的黄斑性黄斑营养不良，常染色体显性遗传性玻璃体脉络膜病变和色素性视网膜炎。其中最常见的是最佳黄斑性黄斑营养不良。Bestrophin 1（Best1）是由BEST1基因编码的蛋白质，自将近20年前首次被发现以来，一直是许多研究的主题。今天我们知道，Best1既是五聚体阴离子通道，又是细胞内Ca ²⁺的调节剂。信号。Best1是一种完整的膜蛋白，它在眼内在视网膜色素上皮细胞中唯一表达，并主要定位在基底外侧质膜上。在大脑中，Best1表达已在神经胶质细胞和星形胶质细胞中均有记载，它们在滋补GABA释放和谷氨酸转运中均起作用。Best1的晶体结构揭示了有关Best1如何充当离子通道以及Ca ²⁺如何起作用的关键信息。调节该功能。使用动物模型进行的研究已使人们对Best1的生理作用产生了深刻的见解，而干细胞技术的进步也使得能够开发出患者来源的“菜中病”模型。在本文中，我们将回顾我们对Best1的了解，并讨论近期临床试验的前景，以测试针对目前尚无法治愈且无法治愈的疾病-贝氏病的疗法。