{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ANKS3 is a multifunctional scaffold protein characterized by ankyrin repeats and a sterile α‐motif (SAM) domain that enables it to form multimeric complexes and mediate critical protein–protein interactions in diverse cellular contexts. Structural and biochemical studies have shown that ANKS3 directly associates with its homolog ANKS6 via SAM–SAM interactions, a partnership that is essential for the assembly of higher‐order macromolecular complexes involved in renal development and ciliary signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " Disruption of ANKS3 function—whether by mutation or reduced expression—leads to defects in ciliary architecture, renal cyst formation, and laterality abnormalities, as demonstrated in zebrafish, mouse models, and human studies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In addition, ANKS3 is implicated in the regulation of kinase localization; for instance, its interaction with NEK7 appears to mediate a post‐translational modification that retains the kinase in the cytoplasm, thereby preventing its aberrant entry into the nucleus."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Beyond its structural role, ANKS3 is also recruited, along with ANKS6 and the RNA‐binding protein BICC1, into stress granules under conditions of translational arrest—suggesting a function in RNA processing and in mounting stress responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In "}, {"type": "i", "children": [{"type": "t", "text": "Caenorhabditis elegans"}]}, {"type": "t", "text": ", the ANKS3 homolog (MLT‐3) operates as part of a conserved NEKL–MLT network that modulates actin dynamics and endocytosis during molting, in cooperation with regulators such as CDC‐42 and its effector kinases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Finally, polymerization screens indicate that ANKS3 is capable of dynamic self‐assembly via its SAM domain, a property that may underlie its ability to nucleate and stabilize signal transduction complexes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Collectively, these findings underscore ANKS3’s versatile role as a molecular scaffold that integrates ciliary function, kidney morphogenesis, and cellular stress responses through its participation in complex protein networks.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n "}, {"type": "b", "children": [{"type": "t", "text": "Keywords:"}]}, {"type": "t", "text": " ANKS3, SAM domain, cilia, renal development, laterality, scaffolding, polymerization, stress granules.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Catherine N Leettola, Mary Jane Knight, Duilio Cascio, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "ANKS3 is mutated in a family with autosomal recessive laterality defect."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-016-1712-4"}], "href": "https://doi.org/10.1007/s00439-016-1712-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27417436"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27417436"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Haribaskar Ramachandran, Christina Engel, Barbara Müller, et al. 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