Core Viewpoint - The study highlights the role of hepatic GPR110 in the sex-specific development of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASH), suggesting it as a potential target for female-specific therapies [4][8]. Group 1: Research Findings - GPR110 is identified as a liver-specific G protein-coupled receptor (GPCR) that is closely related to MASH in a sex-specific manner [6]. - The knockout of the Gpr110 gene in liver cells protects female mice from MASH, while having no effect on male mice [6]. - The variant rs937057 T>C of GPR110 is associated with a higher prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in women [6]. Group 2: Mechanism of Action - GPR110 couples with Gαs to activate protein kinase A (PKA), which induces phosphorylation of NFAT2, inhibiting its nuclear translocation and transcriptional activity, leading to suppression of Esr1 transcription in liver cells [6][8]. - Reducing Gpr110 expression in liver cells improves the liver pathology in female MASH mice, while knocking down estrogen receptor α (Esr1) negates this improvement [6]. Group 3: Implications for Therapy - The findings suggest that inhibiting GPR110 may represent a gender-specific therapeutic approach for MASH, emphasizing the need for targeted treatments based on sex differences [4][8].