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While this poorly conserved domain is known to possess ligand\u2010independent activation function (AF\u20101), few NTD functions are conserved between NRs. Identified roles in other receptors include androgen receptor (AR), estrogen receptor (ER), and mineralocorticoid receptor (MR). Here, we aim to define the function of the NTD of the farnesoid X receptor (FXR), a crucial regulator of lipid and bile acid metabolism. We show that the NTD engages in interdomain contact with other FXR domains. We also observe that the NTD interacts directly with coregulator proteins. Using mutagenesis, mammalian two\u2010hybrid assays, mammalian one\u2010hybrid assay, and molecular dynamics (MD) simulations, we identify and validate a novel SXXLF motif in the NTD which mediates interactions with both coregulators and the ligand binding domain. Mutation of the motif induces large changes in conformational and allosteric coupling in FXR. 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