Sox10 belongs to a family of SRY-related high mobility group box-containing (SOX) proteins. It is crucial for neural crest shuttling and development, encoding a transcription factor involved in embryogenesis and cell differentiation [1,2]. Sox10 is associated with multiple pathways related to the development and function of neural crest derivatives and some extraneural crest tissues. Genetic models are valuable for studying its functions.

In vascular smooth muscle cells (VSMCs), Sox10 upregulation is linked to macrophage-like VSMC accumulation and pyroptosis in vitro and in mouse neointimal hyperplasia models. Tumor necrosis factor α (TNF-α)-induced Sox10 lactylation drives VSMC transdifferentiation, contributing to pyroptosis. Sox10 silencing mitigates vascular inflammation and neointimal hyperplasia in RGS5 knockout mice, suggesting it is a regulator of vascular inflammation [3].

In glioblastoma, low Sox10 expression is linked to neural stem-cell (NSC)-like cell states. Sox10-KD tumors in animal models progress to an aggressive NSC/developmental-like phenotype, and combination treatment using Notch and HDAC/PI3K inhibitors extends the survival of mice with such tumors [4].

In melanoma, loss of Sox10 reduces proliferation, leads to invasive properties, and promotes tolerance to BRAF and/or MEK inhibitors. Targeting SOX10-deficient cells with cIAP1/2 inhibitors combined with BRAF/MEK inhibitors delays acquired resistance in in vivo melanoma models [5].

In conclusion, Sox10 is essential for neural crest-related development and cell differentiation. Model-based research, especially knockout models in mice, has revealed its role in diseases such as vascular inflammation, glioblastoma, and melanoma. These findings provide insights into disease mechanisms and potential therapeutic strategies.