Eya1, belonging to a family of phosphatase-transcriptional activators, lacks intrinsic DNA-binding activity. It is crucial for establishing and maintaining nephron progenitor cells (NPCs) and plays essential roles in progenitor proliferation, cell differentiation and morphogenesis in all three germ layers [1,2]. Eya1 is involved in multiple biological processes such as inner ear development through interacting with SIX1 to form transcriptional activation complexes regulating cell proliferation, survival and neurosensory fate induction [3]. It also impacts cell migration and tumor metastasis in hepatocellular carcinoma [4].

In NPCs, Eya1 interacts with REST corepressors and REST-binding sequences to exert transcriptional repressive activity, and modifies chromatin structure by interacting with chromatin-remodeling factors and specialized DNA-binding proteins to maintain the cellular state of NPCs [1]. In Xenopus laevis, Eya1 protein is expressed in various tissues during embryonic development, with its subcellular localization in both nuclei and cytoplasm [2]. In the mammalian inner ear, mutations of Eya1 gene cause profound developmental auditory defects [3]. In hepatocellular carcinoma, Eya1 promotes cell migration and invasion by activating FNDC3B [4].

In conclusion, Eya1 is a key regulator in multiple biological processes, especially in embryonic development, inner ear formation and cancer progression. Research on Eya1, including through gene-knockout or conditional-knockout mouse models (not directly mentioned in the given references but inferred as valuable based on general gene-function research approach), helps understand its functions in normal development and disease conditions such as auditory defects and hepatocellular carcinoma metastasis.