{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have identified TASL, a protein encoded by CXorf21, as a pivotal adaptor within the endolysosomal toll‐like receptor (TLR) machinery. TASL interacts with the endolysosomal transporter SLC15A4 and harbors a conserved pLxIS motif that mediates the recruitment and activation of the transcription factor IRF5 following TLR7, TLR8, and TLR9 ligation. The absence of TASL selectively disrupts the IRF signalling cascade while leaving NF-κB and MAPK pathways intact, thereby establishing TASL as a dedicated mediator that links ligand recognition to type I interferon responses in innate immunity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther insights into the CXorf21/TASL axis reveal a sexually dimorphic expression pattern where increased levels in immune cells contribute to heightened inflammatory responses. Investigations have demonstrated that CXorf21, which escapes X-chromosome inactivation, is upregulated upon TLR7 stimulation and is expressed more robustly in cells derived from females and systemic lupus erythematosus (SLE) patients. Functional studies illustrate that downregulation of TASL/CXorf21 results in diminished IFNA1 induction and reduced secretion of pro-inflammatory cytokines, implicating its role in the pathogenesis of SLE and highlighting its importance in modulating lysosomal pH in a sex-specific manner."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in immune cells, TASL has emerged as a critical regulator of epidermal homeostasis. Recent findings indicate that TASL deficiency in keratinocytes impairs cell proliferation and migration by inducing G1/S cell cycle arrest and disrupts proper differentiation, in part through the modulation of lysosomal function and calcium signalling. These data extend the functional significance of TASL to skin biology, suggesting that it may influence both immune responses and epithelial cell behaviour."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Leonhard X Heinz, JangEun Lee, Utkarsh Kapoor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41586-020-2282-0"}], "href": "https://doi.org/10.1038/s41586-020-2282-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32433612"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32433612"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Christopher A Odhams, Amy L Roberts, Susan K Vester, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interferon inducible X-linked gene CXorf21 may contribute to sexual dimorphism in Systemic Lupus Erythematosus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-10106-2"}], "href": "https://doi.org/10.1038/s41467-019-10106-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31092820"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31092820"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Valerie M Harris, Kristi A Koelsch, Biji T Kurien, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of cxorf21 Provides Molecular Insight Into Female-Bias Immune Response in SLE Pathogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2019.02160"}], "href": "https://doi.org/10.3389/fimmu.2019.02160"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31695690"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31695690"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ji Yeong Park, Hyeng-Soo Kim, Hyejin Hyung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TASL mediates keratinocyte differentiation by regulating intracellular calcium levels and lysosomal function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-024-61674-3"}], "href": "https://doi.org/10.1038/s41598-024-61674-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38744928"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38744928"}]}]}]}