KLHL24基因编码一种泛素化连接酶，能够介导特定底物的降解。我们的研究表明该基因的突变可以引起大疱性表皮松解症，患者主要表现为皮肤脆性增加、脱发和色素异常；制备的基因敲入小鼠也有明显的毛发减少及色素减退；突变的KLHL24自身泛素化降解受到抑制，变得更稳定；其泛素化底物是角蛋白14，它的过度降解导致了皮肤的脆性增加。此发现首次揭示了KLHL24对于皮肤的生物学功能具有重要的调节作用，而KLHL24影响伤口愈合、毛囊生理和色素分布的分子机制是我们进一步关注的科学问题。我们最近的实验并结合目前的文献分析提示，KLHL24很可能通过调节Wnt信号通路影响以上的皮肤功能。本研究拟在分子、细胞、动物和人体水平，系统揭示KLHL24调控Wnt信号通路在伤口愈合、毛囊发育和色素分布中的作用，为阐明KLHL24的生物学功能及通过调节泛素化来治疗一些皮肤病提供新的理论基础。

KLHL24 gene encodes an ubiquitin ligase substrate receptor, mediating the degradation of specific substrates. Our recent research found that start-codon mutations of KLHL24 can cause epidermolysis bullosa (EB). The main manifestations of this new type of EB are skin fragility, alopecia and dyspigmentation, while the knock-in mouse model also show pronounced hair loss and hair graying. We found the mutant KLHL24 protein is more stable than wild-type protein due to abolished autoubiquitination, leading to excessive degradation of keratin 14, a substrate of KLHL24, causing skin fragility. Our findings revealed that KLHL24 plays an important role in the regulation of skin biological functions for the first time. On the next step, we will focus on exploring the molecular mechanisms of KLHL24 in regulating wound healing, hair follicle biology and pigmentation. Our latest results and literatures analysis indicate that KLHL24 may influence those skin biological functions by regulating Wnt signaling pathway. We will study the regulatory role of KLHL24 in Wnt signaling pathway during wound healing, hair follicle development and pigmentation process at molecular and cellular level and further in animal and human. Our research will elucidate the biological functions of KLHL24, and provide new theoretical basis for treating skin disorders via regulation of ubiquitin-proteasome system.