{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nWWC1, which encodes the protein KIBRA, plays a pivotal role in the neural circuitry underlying human memory. In the brain, KIBRA is highly expressed in memory‐related regions and regulates synaptic plasticity through its interactions with proteins such as PICK1 and AMPA receptors, thereby modulating receptor trafficking, actin remodeling, and long‐term potentiation. Genetic studies have repeatedly linked polymorphisms in WWC1—notably the rs17070145 variant—to variations in episodic and spatial memory performance, differences in hippocampal activation and structure, and even an altered risk for Alzheimer's disease. In some cohorts, T‐allele carriers show enhanced recall and connectivity, whereas other studies report more complex, sometimes negligible effects on global cognitive ability and neurodegeneration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its neuronal functions, KIBRA is integral to multiple signaling pathways that govern cellular proliferation, survival, and polarity. It operates as an upstream regulator of the Hippo pathway by directly associating with and activating LATS kinases, thereby facilitating the phosphorylation and regulation of the key effector YAP. In addition, KIBRA interacts with several other signaling components—including PTPN14, protein kinase C zeta, and members of the PAR3–aPKC–PAR6 polarity complex as well as the tyrosine kinase DDR1—to influence epithelial cell polarity, cell–cell adhesion, and motility. These interactions extend KIBRA’s relevance to neurodevelopmental conditions such as Tourette disorder and further underscore its versatile role in modulating cell signaling networks."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nKIBRA is also subject to intricate post‐translational regulation that fine‐tunes its cellular functions. It is phosphorylated by several mitotic kinases—including Aurora-A/B, members of the ERK–RSK cascade, and CDK1—which modulate its activity during cell cycle progression, mitosis, and in the maintenance of tight junctions and epithelial polarity. Altered expression and epigenetic silencing of WWC1 have been observed in various cancers, with studies implicating KIBRA in both tumor-suppressive and oncogenic roles in breast, prostate, and lung adenocarcinomas. In addition, through its regulation of downstream effectors such as YAP, KIBRA contributes to the maintenance of podocyte integrity in the kidney, further highlighting its diverse roles in cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "24", "end_ref": "35"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Andreas Papassotiropoulos, Dietrich A Stephan, Matthew J Huentelman, et al. 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