Twist-related protein 2 encoded by TWIST2 gene is a transcription factor that regulates gene expression during the differentiation of mesenchymal cells. Specifically, it directs the development of dermal and chondrogenic tissues. Additionally, during osteoblast development, TWIST2 protein is also known to be involved in inhibition of osteoblast maturation and maintenance of cells in a preosteblast phenotype. Structurally, the protein is a basic helix-loop-helix (bHLH) transcription factor, and shares similarity with other bHLH transcription factors.

Mutations in TWIST2 are known to cause Setleis Syndrome, a type of focal facial dermal dysplasia. TWIST2 is also implicated in several cancers, especially breast and cervical cancers, by way of their mediation in epithelial-mesenchymal transitions. TWIST2 expression has been found to be correlated with tumor histological type and metastasis of breast cancer, and thus can be used as a potential diagnostic biomarker of breast carcinomas. Upregulation of TWIST2 is also correlated with very poor prognosis in head and neck cancer patients.