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Their therapeutic relevance has long been attributed to retinoic acid receptor (RAR)-mediated transcriptional activity; however, recent studies have revealed additional layers of regulation, including epigenetic modifications, kinase signaling networks, and interactions with the skin microbiome. These mechanisms not only refine our understanding of retinoid function but also inform strategies to overcome therapeutic limitations such as resistance, irritation, and systemic toxicity. Advances in medicinal chemistry have yielded synthetic retinoids with enhanced receptor selectivity, particularly for RAR-\u03b3 agonists such as trifarotene, as well as inhibitors of cytochrome P450\u2013mediated retinoic acid metabolism, which sustain endogenous activity and mitigate resistance (DX314 and other RAMBAs). In parallel, the development of nanocarriers, stimuli-responsive gels, and other targeted delivery systems has improved drug stability, bioavailability, and tolerability. Together, these innovations underscore the evolving role of retinoid-based interventions in precision dermatology, providing opportunities to optimize treatment outcomes for acne, psoriasis, photoaging, and other dermatological disorders while addressing the shortcomings of earlier generations.<\/jats:p>","DOI":"10.3390\/cells14211650","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T01:14:02Z","timestamp":1761182042000},"page":"1650","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Next Generation of Skin Care: Transforming Retinoid Therapeutics"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0631-4846","authenticated-orcid":false,"given":"Julia Weronika","family":"\u0141uczak","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Post\u0119pu 36A, 05-552 Magdalenka, Poland"},{"name":"Department of Nanobiotechnology, Institute of Biology, Warsaw University of Life Sciences, Ciszewskiego 8, Bldg. 23, 02-786 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0399-5280","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Palusi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Post\u0119pu 36A, 05-552 Magdalenka, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Ma\u015bli\u0144ska-Gromadka","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Post\u0119pu 36A, 05-552 Magdalenka, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6198-9449","authenticated-orcid":false,"given":"Damian","family":"Pietrzak","sequence":"additional","affiliation":[{"name":"Chair of Drug and Cosmetics Biotechnology, Faculty of Chemistry, Warsaw University of Technology, Koszykowa 75 Street, 00-662 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Szopi\u0144ski","sequence":"additional","affiliation":[{"name":"Institute of Clinical Sciences, Maria Sklodowska-Curie Medical Academy in Warsaw, Pl. \u017belaznej Bramy 10, 00-136 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0539-0680","authenticated-orcid":false,"given":"S\u0142awomir","family":"Lewicki","sequence":"additional","affiliation":[{"name":"Institute of Outcomes Research, Maria Sklodowska-Curie Medical Academy, Pl. \u017belaznej Bramy 10, 00-136 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tino","family":"Schenk","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Clinic of Internal Medicine II, Jena University Hospital, 07747 Jena, Germany"},{"name":"Institute of Molecular Cell Biology, Center for Molecular Biomedicine Jena (CMB), Jena University Hospital, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0148-541X","authenticated-orcid":false,"given":"\u0141ukasz","family":"Szyma\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Post\u0119pu 36A, 05-552 Magdalenka, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Szyma\u0144ski, \u0141., Skopek, R., Palusi\u0144ska, M., Schenk, T., Stengel, S., Lewicki, S., Kraj, L., Kami\u0144ski, P., and Zelent, A. 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