{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n EPS8L2, a member of the Eps8 family of actin‐regulatory proteins, has emerged as a key factor in maintaining the integrity and function of mechanosensory structures. In inner ear hair cells, EPS8L2 localizes to the tips of stereocilia in both the cochlea and vestibule, where it is not required for the initial elongation (a role served by its homolog EPS8) but is essential for the long‐term maintenance of the characteristic “staircase” organization and mechano‐electrical transduction. Loss‐of‐function mutations or inframe deletions in EPS8L2 lead to a gradual deterioration in stereocilia morphology and are associated with progressive, late‐onset hearing loss in mice, humans, and even canine models of early onset adult deafness."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, EPS8L2 associates with other proteins within specialized stereociliary complexes. For example, it forms part of the so-called “row 2” complex—interacting with proteins such as BAIAP2L2—to help maintain the mechanotransducing stereocilia and proper localization of actin regulators."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its well‐established role in the auditory system, EPS8L2 has been implicated in other cellular contexts. Transcriptomic studies identified EPS8L2 among p53‐regulated genes following chemotherapeutic stress, suggesting it may play a role in apoptotic or stress responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In the realm of cancer immunotherapy, an EPS8L2‐derived peptide has been proposed as a potential off‐target responsible for neurotoxicity in a MAGE-A3 targeted therapy, prompting caution in designing such T-cell receptor approaches."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, altered expression levels of EPS8L2 have been documented in patient samples from clear cell renal cell carcinoma, where its elevated expression is associated with tumor progression and may serve as a noninvasive urinary biomarker to distinguish aggressive disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Similarly, EPS8L2 is included in panels of candidate biomarkers for lupus nephritis, highlighting its potential utility in monitoring inflammatory or pathological states."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, while its interactions with other members of the Eps8 family are more robust, EPS8L2 has also been shown to bind modestly to the T cell receptor complex (via CD3ε), hinting at possible, though less pronounced, roles in immune signal modulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, the multifaceted functions of EPS8L2—from maintaining actin‐based stereocilia architecture essential for auditory transduction to its emerging roles in stress response, cancer progression, and immune regulation—underscore its importance in both normal physiology and disease.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "David N Furness, Stuart L Johnson, Uri Manor, et al. 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