En1, short for Engrailed-1, is a homeodomain transcription factor. It is involved in multiple biological processes such as neuronal development in the midbrain, cerebellum, hindbrain and spinal cord, and is associated with pathways like Hedgehog and Wnt signaling. Its role in development and disease makes it an important gene for study, with genetic models like mouse models being valuable tools [2,4].

In a mouse model, conditional loss of En1 (using En1(cre/flox) mice) led to low bone mass, likely due to high bone turnover, indicating its importance in bone density regulation [1]. In superior olivary complex (SOC) neurons, En1 deletion caused aberrant neuron positioning and subsequent death, and also led to failure in expressing the transcription factor FoxP1, revealing its role in SOC neuron development and maturation [4]. In human glioma cells, EN1 was found to regulate cell growth and proliferation via the Hedgehog signaling pathway, and its high expression predicted a worse prognosis [3]. In triple-negative breast cancer (TNBC), down-regulation of EN1 preferentially reduced cell viability and tumorigenicity, and high EN1 expression correlated with short overall survival and increased brain metastasis risk, suggesting it as a prognostic marker and potential therapeutic target [5].

In conclusion, En1 plays essential roles in bone density regulation, neuronal development, and cancer-related processes like glioma cell growth and TNBC progression. Studies using En1 knockout or conditional knockout mouse models have significantly contributed to understanding its functions in these disease-related areas, providing insights into potential therapeutic strategies.