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This review examines the emerging role of long non-coding RNAs (lncRNAs) in psoriasis pathogenesis, highlighting their significance as regulatory molecules in disease initiation, progression, and chronicity. LncRNAs demonstrate distinct expression patterns in psoriatic lesions, with upregulated transcripts such as MALAT1, XIST, MIR31HG, and HOTAIR promoting keratinocyte hyperproliferation, inhibiting apoptosis, and amplifying inflammatory cascades through mechanisms including microRNA sponging and transcription factor modulation. These molecules primarily target key signaling pathways including NF-\u03baB, STAT3, and PI3K\/AKT. Conversely, downregulated lncRNAs like NEAT1, MEG3, and PRINS normally function as tumor suppressor molecules that maintain epidermal homeostasis through pro-apoptotic and anti-inflammatory mechanisms. Their reduced expression contributes to the pathological hyperproliferative phenotype characteristic of psoriatic skin. Importantly, genetic variants within lncRNA loci have been identified as significant contributors to psoriasis susceptibility and treatment responses across different populations. Single- nucleotide polymorphisms in genes such as TRAF3IP2-AS1, HOTAIR, and CDKN2B-AS1 demonstrate population-specific associations with disease risk and therapeutic outcomes, suggesting their potential utility as pharmacogenomic markers. The complex regulatory networks involving lncRNAs provide new insights into psoriasis pathogenesis and offer promising avenues for personalized treatment strategies. Integration of lncRNA profiling into clinical practice may enhance our understanding of disease heterogeneity and improve therapeutic outcomes for psoriatic patients.<\/jats:p>","DOI":"10.3390\/ncrna11050069","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T12:33:32Z","timestamp":1758285212000},"page":"69","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Long Non-Coding RNAs in Psoriasis: A Comprehensive Review of Expression Profiles, Mechanistic Insights, Genetic Associations, and Their Clinical Implications"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0270-5309","authenticated-orcid":false,"given":"Judit","family":"Danis","sequence":"first","affiliation":[{"name":"Department of Immunology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, H-6720 Szeged, Hungary"},{"name":"HUN-REN-SZTE Dermatological Research Group, University of Szeged, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rta","family":"Sz\u00e9ll","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, H-6720 Szeged, Hungary"},{"name":"HUN-REN-SZTE Functional Clinical Genetics Research Group, University of Szeged, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/bjd.19169","article-title":"Systematic review examining changes over time and variation in the incidence and prevalence of psoriasis by age and gender","volume":"184","author":"Iskandar","year":"2021","journal-title":"Br. 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