Atoh8, also named Math6, belongs to the basic helix-loop-helix (bHLH) protein superfamily of transcriptional regulators. These bHLH proteins are involved in embryonic development, disease initiation and progression, and their translation, location, and turnover are tightly regulated. Atoh8 functions as both a transcriptional activator and repressor, and is associated with multiple diseases. It plays roles in embryonic development and carcinogenesis, mainly acting as a tumor suppressor [1].

In mouse models, targeted deletion of Atoh8 leads to severe hearing loss, indicating its importance in normal hearing development, though the exact function remains to be elucidated [4]. In chondrogenesis, deleting Atoh8 in mice using chondrocyte-specific (Atoh8flox/flox;Col2a1-Cre) and germline-specific (Atoh8flox/flox;Prx1-Crefemale) Cre alleles results in reduced skeletal size of axial and appendicular bones, with different stages of phenotypic manifestations. It is identified as a positive regulator of chondrocyte proliferation, acting on chondrocyte proliferation in parallel or downstream of Ihh signaling and on the onset of hypertrophy upstream of Ihh [3]. Depleting Atoh8 rapidly accelerates oncogenic Ras-driven lung tumorigenesis, suggesting its role in preventing Ras-driven malignant transformation [2].

In conclusion, Atoh8 is crucial in multiple biological processes. Its functions in embryonic development, especially in the development of the inner ear and chondrogenesis, are well-demonstrated through gene knockout mouse models. In disease, Atoh8 plays a significant role in cancer prevention, such as in lung cancer prevention by inhibiting Ras-driven transformation. These findings from model-based research enhance our understanding of its biological functions and potential in disease-related research.