{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMBOAT4, which encodes ghrelin O‐acyltransferase (GOAT), is an integral membrane enzyme that catalyzes the unique posttranslational acylation of the peptide hormone ghrelin at serine‐3. This octanoylation reaction is essential for ghrelin’s biological activity—enabling it to bind its receptor and regulate feeding, energy balance, and endocrine functions. The discovery and molecular characterization of GOAT reveal that it is a member of the membrane‐bound O‐acyltransferase (MBOAT) family, and its acyltransferase activity is critical for generating the active, acylated form of ghrelin from its inactive precursor."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural and biochemical analyses indicate that GOAT possesses multiple transmembrane domains—with topology predictions suggesting as many as 11 helices—and exhibits a marked substrate specificity for an eight‐carbon acyl donor, despite reported acyl donor promiscuity. GOAT is widely expressed in ghrelin‐producing tissues (such as the stomach, gut, and pituitary) and is also present in the circulation, suggesting its roles extend beyond local ghrelin acylation. These insights highlight GOAT’s suitability as a therapeutic target for conditions like obesity and diabetes, as well as its potential utility in inhibitor design."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent translational studies have further explored GOAT’s role as a biomarker and pharmacological target. Assays developed to measure GOAT activity in tissues and plasma support its metabolic regulation, with altered plasma levels observed in conditions ranging from anorexia to morbid obesity as well as in certain cancers. Moreover, the identification of potent small‐molecule inhibitors of GOAT underscores its druggability and therapeutic potential in modulating ghrelin signaling for the treatment of metabolic disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "14"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jesus A Gutierrez, Patricia J Solenberg, Douglas R Perkins, et al. 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