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This review synthesizes new insights that have revolutionized our understanding of the molecular and biological functions of TRIM\u2010NHL proteins. Multiple TRIM\u2010NHLs have been shown to bind specific RNA sequences and structures. X\u2010ray crystal structures of TRIM\u2010NHL proteins in complex with RNA ligands reveal versatile modes of RNA recognition by the NHL domain. Functional and genetic analyses show that TRIM\u2010NHL RNA\u2010binding proteins negatively regulate the protein expression from the target mRNAs that they bind. This repressive activity plays a crucial role in controlling stem cell fate in the developing brain and differentiating germline. To highlight these paradigms, we focus on several of the most\u2010extensively studied TRIM\u2010NHL proteins, specifically\n                    <jats:italic>Drosophila<\/jats:italic>\n                    and vertebrate TRIM71, among others. Brat is essential for development and regulates key target mRNAs to control differentiation of germline and neural stem cells. TRIM71 is also required for development and promotes stem cell proliferation while antagonizing differentiation. Moreover, TRIM71 can be utilized to help reprogram fibroblasts into induced pluripotent stem cells. Recently discovered mutations in TRIM71 cause the neurodevelopmental disease congenital hydrocephalus and emphasize the importance of its RNA\u2010binding function in brain development. Further relevance of TRIM71 to disease pathogenesis comes from evidence linking it to several types of cancer, including liver and testicular cancer. Collectively, these advances demonstrate a primary role for TRIM\u2010NHL proteins in the post\u2010transcriptional regulation of gene expression in crucial biological processes.\n                  <\/jats:p>\n                  <jats:p>\n                    This article is categorized under:\n                    <jats:list list-type=\"simple\">\n                      <jats:list-item>\n                        <jats:p>RNA Interactions with Proteins and Other Molecules &gt; Protein\u2010RNA Interactions: Functional Implications<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Translation &gt; Translation Regulation<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>RNA Turnover and Surveillance &gt; Regulation of RNA Stability<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  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