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Its biological and pathological effects are determined by cell lineage, ligand presentation, and mutational context. At the pathway level, SCF expression and processing, KIT abundance, and activating mutations determine signal initiation and intensity, whereas CBL-mediated receptor degradation and SHP-1-mediated dephosphorylation limit signal duration. This narrative review critically examines representative multisystem diseases for which SCF\/KIT involvement is supported by genetic, functional, or therapeutic evidence and distinguishes established treatments from investigational approaches. Activating KIT mutations drive gastrointestinal stromal tumors (GISTs) and systemic mastocytosis. Clinically established KIT-directed tyrosine kinase inhibitors, including imatinib for mutation-sensitive GIST and midostaurin or avapritinib for advanced systemic mastocytosis, have transformed disease management. By contrast, increased local SCF availability and KIT-dependent mast cell persistence may amplify inflammatory diseases, whereas impaired signaling is associated with gastrointestinal dysmotility, reproductive dysfunction, and pigmentary abnormalities. Emerging anti-KIT antibodies are being investigated as a strategy to deplete mast cells in chronic urticaria, whereas recombinant SCF-based mobilization has largely historical clinical relevance and regenerative applications remain experimental. Mutation-dependent drug sensitivity, polyclonal secondary resistance, multikinase-related toxicity, and on-target effects in normal KIT-dependent tissues remain major challenges. A disease-, genotype-, and cell-specific framework is therefore essential for translating SCF\/KIT biology into safe and effective precision therapies.<\/jats:p>","DOI":"10.1177\/00368504261492893","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:23:41Z","timestamp":1790684621000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["The SCF\/KIT signaling pathway in multisystem diseases: Mechanisms and therapeutic targeting"],"prefix":"10.1177","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6400-3353","authenticated-orcid":false,"given":"Ruidie","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Nephrology and Rheumatology, Zhaotong Hospital of Traditional Chinese Medicine, Zhaotong, Yunnan, China."},{"name":"School of Chinese Medicine, Hubei University of Chinese Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueliang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Rheumatology, Zhaotong Hospital of Traditional Chinese Medicine, Zhaotong, Yunnan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingbing","family":"Mei","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Hubei University of Chinese Medicine"},{"name":"Department of Geriatrics, Hubei Provincial Hospital of Traditional Chinese Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(99)00076-X"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00046.2011"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.04.012"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-016-0120-8"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5350.577"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26118"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2008.01109.x"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/all.15585"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0042-1"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.263830"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.3.641.bloodjournal853641"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-7-90"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.1177\/42.11.7523489"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20929"},{"key":"e_1_3_7_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601545"},{"key":"e_1_3_7_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-004-4189-6"},{"key":"e_1_3_7_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.4.2089"},{"key":"e_1_3_7_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-05-1768"},{"key":"e_1_3_7_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(99)00078-3"},{"key":"e_1_3_7_21_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0044-1789204"},{"key":"e_1_3_7_22_2","doi-asserted-by":"publisher","DOI":"10.1177\/17588359231192388"},{"key":"e_1_3_7_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-024-01272-7"},{"key":"e_1_3_7_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10120-025-01639-1"},{"key":"e_1_3_7_25_2","doi-asserted-by":"publisher","DOI":"10.2147\/JBM.S366367"},{"key":"e_1_3_7_26_2","first-page":"2048","article-title":"Systemic mastocytosis: current status and challenges in 2024","volume":"9","author":"Ustun C","year":"2025","unstructured":"Ustun C, Keklik Karadag F, Linden MA, et al. 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