biostudies-literatureZhong TNational Natural Science Foundation of China1719-1729https://www.ebi.ac.uk/biostudies/studies/S-EPMC9433399biostudies-literatureUnknown29(9)Stratification of the epidermis is essential for the barrier function of the skin. However, the molecular mechanisms governing epidermal stratification are not fully understood. Herein, we demonstrate that enkurin domain-containing protein 1 (ENKD1) contributes to epidermal stratification by modulating the cell-division orientation of basal keratinocytes. The epidermis of Enkd1 knockout mice is thinner than that of wild-type mice due to reduced generation of suprabasal cells from basal keratinocytes through asymmetric division. Depletion of ENKD1 impairs proper orientation of the mitotic spindle and delays mitotic progression in cultured cells. Mechanistic investigation further reveals that ENKD1 is a novel microtubule-binding protein that promotes the stability of astral microtubules. IntCell death and differentiationENKD1 promotes epidermal stratification by regulating spindle orientation in basal keratinocytes.PMC94333993200087031730050321708293207070832000490Xie WLi DLiu MZhong TSun SSong TLuo YLuo XXie SWu XZhou JfalseENKD1 promotes epidermal stratification by regulating spindle orientation in basal keratinocytes.Stratification of the epidermis is essential for the barrier function of the skin. However, the molecular mechanisms governing epidermal stratification are not fully understood. Herein, we demonstrate that enkurin domain-containing protein 1 (ENKD1) contributes to epidermal stratification by modulating the cell-division orientation of basal keratinocytes. The epidermis of Enkd1 knockout mice is thinner than that of wild-type mice due to reduced generation of suprabasal cells from basal keratinocytes through asymmetric division. Depletion of ENKD1 impairs proper orientation of the mitotic spindle and delays mitotic progression in cultured cells. Mechanistic investigation further reveals that ENKD1 is a novel microtubule-binding protein that promotes the stability of astral microtubules. Int2022-01-01T00:00:00Z2022 Sep2025-04-04T12:27:32.605Z2025-04-04T12:27:32.605ZS-EPMC94333993519756510.1038/s41418-022-00958-5