TEAD1, or TEA domain transcription factor 1, is a crucial transcription factor in the Hippo pathway, which regulates cellular proliferation, organ size, and tissue homeostasis [1,2,3,4,5,6,7,8,9]. It plays a vital role in multiple biological processes including heart development, homeostasis, and cell survival, and is associated with various diseases such as liver fibrosis, heart failure, and dilated cardiomyopathy [1,2,3,4]. Genetic models, like gene knockout (KO) and conditional knockout (CKO) mouse models, have been instrumental in studying its functions.

In liver, deletion of TM7SF3 accelerates hepatic stellate cell (HSC) activation, promoting alternative splicing of TEAD1 and generating a more active form, which triggers HSC activation and liver fibrosis. Inhibiting TEAD1 alternative splicing can reduce liver fibrosis [1]. In the heart, conditional TEAD1 knockout in cardiac fibroblasts and myofibroblasts ameliorates pressure overload-induced cardiac remodeling [2]. Ubiquitous or cardiomyocyte-specific Tead1 loss in adult mice leads to acute-onset dilated cardiomyopathy due to activation of the necroptotic pathway in cardiomyocytes [6]. Also, perinatal cardiomyocyte-specific deletion of Tead1 causes lethal dilated cardiomyopathy by postnatal day 9, as Tead1-deficient cardiomyocytes have decreased proliferation [9].

In conclusion, TEAD1 is essential for normal cell proliferation, especially in cardiomyocytes during the perinatal period, and its dysregulation contributes to the development of liver fibrosis and various heart diseases. Studies using KO and CKO mouse models have significantly enhanced our understanding of TEAD1's functions in these disease-related biological processes, providing potential therapeutic targets for treatment.