Erythrocyte protein band 4.1 like 5 (EPB41L5) is an adaptor protein beneath the plasma membrane that functions to control epithelial morphogenesis. Here we report a previously uncharacterized role of EPB41L5 in controlling ciliary function. We found that EPB41L5 forms a complex with IQCB1 (previously known as NPHP5), a ciliopathy protein. Overexpression of EPB41L5 reduced IQCB1 localization at the ciliary base in cultured mammalian epithelial cells. Conversely, epb41l5 knockdown increased IQCB1 localization at the ciliary base. epb41l5-deficient zebrafish embryos or embryos expressing C-terminally modified forms of Epb41l5 developed cilia with reduced motility and exhibited left–right patterning defects, an outcome of abnormal ciliary function. We observed genetic synergy between epb41l5 and iqcb1. Moreover, EPB41L5 decreased IQCB1 interaction with CEP290, another ciliopathy protein and a component of the ciliary base and centrosome. Together, these observations suggest that EPB41L5 regulates the composition of the ciliary base and centrosome through IQCB1 and CEP290.

红细胞蛋白带 4.1 样 5 (EPB41L5) 是质膜下方的一种接头蛋白，其功能是控制上皮形态发生。在这里，我们报告了 EPB41L5 在控制纤毛功能中以前未表征的作用。我们发现 EPB41L5 与纤毛病蛋白 IQCB1（以前称为 NPHP5）形成复合物。EPB41L5 的过度表达减少了培养的哺乳动物上皮细胞中 IQCB1 在睫状基部的定位。相反，epb41l5敲除增加了 IQCB1 在睫状基部的定位。epb41l5-缺陷的斑马鱼胚胎或表达C端修饰形式的Epb41l5的胚胎发育出运动性降低的纤毛，并表现出左右图案缺陷，这是纤毛功能异常的结果。我们观察到epb41l5和iqcb1 之间的遗传协同作用。此外，EPB41L5 降低了 IQCB1 与 CEP290 的相互作用，CEP290 是另一种纤毛病蛋白，也是纤毛基部和中心体的组成部分。总之，这些观察结果表明 EPB41L5 通过 IQCB1 和 CEP290 调节睫状基部和中心体的组成。