表皮成熟过程中，基底层的祖细胞不断分裂促使表皮分层和分化。细胞分裂的方向取决于纺锤体定向，进而影响表皮细胞分层和分化成熟。我们前期通过组学分析鉴定得到了ENKD1蛋白，发现其缺失影响基底层细胞的纺锤体定向及表皮分层。根据初步的探究结果发现ENKD1结合微管并影响皮层极性蛋白的定位，星体微管和细胞皮层的相互作用则对调控纺锤体定向至关重要。据此我们提出“ENKD1作为微管结合蛋白，通过影响星体微管的稳定性和定位以及皮层极性蛋白复合物的定位，参与调控纺锤体定向，进而影响基底层细胞分裂和表皮成熟”的科学假设。本课题将探究ENKD1在基底层细胞分化中的关键作用，分析ENKD1对纺锤体定向的具体影响，并从其对星体微管及对皮层极性蛋白的调控机制两方面进行解释。这对阐明ENKD1如何调控纺锤体定向，进而影响表皮分层及成熟表皮的形成非常重要，对研究表皮发育相关疾病及纺锤体定向异常的疾病具有重要意义。

The epidermal maturation is tightly controlled during embryogenesis. In the developing epidermis, the progenitor cells undergo cell division to generate differentiated cell layers. The direction of cell division, which is dependent on spindle orientation, is crucial for epidermal cell stratification and differentiation. In order to further explore the regulatory mechanism of epidermal stratification, we conducted transcriptome analysis and carried out preliminary experiments. These results shown that ENKD1 affects the spindle orientation and epidermal stratification of keratinocytes, but the detailed mechanism is still unclear. Preliminary mechanism exploration revealed that ENKD1 binds microtubules and affects the localization of cortical polarity protein complex, while the interaction between astral microtubules and cellular cortex is important in regulating spindle orientation. Accordingly, we proposed the scientific hypothesis that "ENKD1, as a microtubule-binding protein, is involved in regulating spindle orientation by affecting the stability and localization of astral microtubules and the localization of cortical polar protein complexes, thus affecting basal cell division and epidermal maturation". We will explore the key role of ENKD1 in basal cell differentiation, analyze the regulation of ENKD1 on spindle orientation, and explain the regulatory mechanism of ENKD1 on astral microtubules and cortical polar proteins. This is of great importance to elucidate how ENKD1 regulates spindle orientation, thereby affecting epidermal stratification and maturation of epidermis, and is of great significance to the study of epidermal development and abnormal spindle orientation related diseases.