HNF4G (hepatocyte nuclear factor 4 gamma) is a transcription factor that regulates tissue-specific gene expression and cellular differentiation across multiple organ systems. In the intestine, HNF4G works together with HNF4A to regulate fatty acid oxidation genes including Acsl5, Acsf2, Slc27a2, Fabp2, and Hadh, which are essential for intestinal stem cell renewal 1. The protein facilitates CD4+CD8αα+ intraepithelial lymphocyte development by modulating interleukin-18 signaling, and its deletion in T cells leads to early mortality from intestinal pathogen infection 2. In cancer contexts, HNF4G functions as a driver transcription factor in primary pancreatic ductal adenocarcinoma, with its expression or activity decreasing in advanced disease to unmask FOXA1's metastatic potential 3. Additionally, β-catenin activation suppresses HNF4G expression in colon cancer, contributing to immune evasion by reducing butyrophilin-like molecule expression and γδ T-cell infiltration 4. HNF4G also promotes hepatocyte marker expression in cholangiocytes during transdifferentiation, involving genome-wide chr8 reorganization 5. In kidney development, HNF4G shows functional redundancy with HNF4A, with less critical roles in human proximal tubule differentiation 6. Genetic variants in HNF4G, particularly rs2941484 TT genotype, are associated with hyperuricemia risk in Chinese Han men 7.