{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPRICKLE1 is a core component of the planar cell polarity (PCP) machinery that modulates noncanonical Wnt signaling. In Drosophila, Prickle interacts with Strabismus to affect Frizzled/Dishevelled activity by controlling its own and adjacent protein membrane localization, a mechanism essential for symmetry‐breaking during ocular development ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "]. In vertebrates, conserved domains (including the PET, LIM, and PKH regions) mediate these interactions, while phosphorylation by the Ste20 kinase Mink1 regulates Prickle’s Rab5‐dependent endosomal trafficking—a process that underscores its asymmetric accumulation at the plasma membrane during convergent extension and cell polarity establishment ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "]. In addition, PRICKLE1 modulates beta‐catenin–independent signaling as evidenced by its role in hepatocellular carcinoma, highlighting its broader regulatory influence on tissue morphogenesis and signaling cascades ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "].\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the nervous system, altered PRICKLE1 function has been associated with a spectrum of neurological disorders. Mutations in PRICKLE1 disrupt its interaction with REST/NRSF—also referred to as RILP—contributing to progressive myoclonus epilepsy, ataxia, and seizure phenotypes observed in humans, mice, flies, and zebrafish models ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "]. Furthermore, rare heterozygous missense changes in PRICKLE1 predispose to neural tube defects, while its binding to REST and synaptic proteins such as SYNAPSIN I appears critical for the regulation of synaptic vesicle dynamics and proper neuronal gene expression—a disruption that is implicated in autism spectrum disorders ["}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "]. This regulatory role is further supported by evidence linking alterations in neuronal-specific gene expression, such as that of tyrosine hydroxylase, to the broader REST network ["}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "13"}]}, {"type": "t", "text": "].\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond development and neural regulation, aberrant PRICKLE1 expression contributes to cancer progression. By binding to kinases such as MINK1 and through its interaction with RICTOR, a member of the mTORC2 complex, PRICKLE1 influences AKT activation and the dynamics of focal adhesions—thereby promoting cell migration and metastatic dissemination in breast cancer and other solid tumours ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "]. In gastric cancer cells, PRICKLE1 localizes to cell retraction sites to facilitate focal adhesion disassembly via association with CLASPs and LL5β, a mechanism that is mirrored by its upregulation in triple-negative breast cancers and acute myeloid leukemia where high expression correlates with poor prognosis ["}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "17"}]}, {"type": "t", "text": "]. Emerging genome-wide association studies further suggest that PRICKLE1 might be linked to broader metabolic pathways, including those involved in type 2 diabetes ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "].\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Andreas Jenny, Rachel S Darken, Paul A Wilson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prickle and Strabismus form a functional complex to generate a correct axis during planar cell polarity signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/emboj/cdg424"}], "href": "https://doi.org/10.1093/emboj/cdg424"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12941693"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12941693"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Masuko Katoh, Masaru Katoh "}, {"type": "b", "children": [{"type": "t", "text": "Identification and characterization of human PRICKLE1 and PRICKLE2 genes as well as mouse Prickle1 and Prickle2 genes homologous to Drosophila tissue polarity gene prickle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Med (2003)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12525887"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12525887"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Avais M Daulat, Olivia Luu, Anson Sing, et al. 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