{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Immediate early response 5–like (IER5L) is a member of the immediate early response gene family that appears to function as a target‐specific regulator of protein phosphatase 2A (PP2A) activity, thereby influencing key signaling pathways that govern cell proliferation, differentiation, and stress responses. In colon cancer cells, for example, enhanced differentiation induced by insulin‐like growth factor binding protein–related protein 1 is accompanied by downregulation of IER5L expression, suggesting that reduced IER5L levels may favor a more differentiated cellular phenotype ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "]. In parallel, functional studies have demonstrated that the conserved N‐terminal region of IER5L is critical for its interaction with PP2A complexes, with IER5L promoting the dephosphorylation of specific targets such as heat shock factor 1 (HSF1) and ribosomal protein S6 kinase, in addition to mediating conversion of the cell cycle regulator CDC25A into its hypophosphorylated form—actions that collectively modulate cell cycle progression ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "]. Beyond cancer cell biology, genetic association and transcriptomic studies have implicated IER5L in a range of physiological and pathological contexts. For instance, IER5L has been identified in expression quantitative trait loci (eQTL) analyses in porcine muscle, linking it to traits such as feed efficiency and suggesting a role in metabolic regulation ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "]. In a clinical context, analyses of gene expression in age‐related macular degeneration nominated IER5L as a promising diagnostic biomarker that correlates with immune cell infiltration in affected tissues ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "]. Moreover, population‐genetic studies have provided evidence that IER5L is under recent positive selection in certain human groups—hinting at its involvement in pathways related to cellular differentiation and apoptosis ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "]. Nutritional intervention studies further reveal that IER5L is among the immune‐related genes whose transcriptional response is enhanced by omega‑3 polyunsaturated fatty acid consumption during inflammatory challenges, thereby implicating it in immune modulation ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "]. Finally, network analyses in glioblastoma have surfaced IER5L as a hub gene within regulatory modules associated with disease progression, underscoring its potential relevance as a molecular marker in tumor biology ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "].\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wenjing Ruan, Shuzhen Zhu, Haibing Wang, et al. 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