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Single\u2010cell RNA\u2010sequencing (scRNA\u2010seq) has provided unprecedented insights into cellular heterogeneity in IC\/BPS. This review summarizes recent scRNA\u2010seq findings on bladder cell populations, emphasizing urothelial, interstitial and immune cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A comprehensive analysis of published scRNA\u2010seq studies was conducted to compare bladder cell subtypes in healthy and IC\/BPS\u2010affected bladders. Differences between IC\/BPS patients and mouse models, as well as sex\u2010specific cellular variations, were examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IC\/BPS bladders exhibit significant urothelial alterations, including a reduction in UPK3A\u2009+\u2009umbrella cells and an expansion of progenitor\u2010like cells with impaired regenerative capacity, linked to TLR3\u2010NR2F6 signalling. Interstitial cells include three fibroblast subtypes (PDGFRA+, RGS5+ and pro\u2010inflammatory IL6\u2010producing fibroblasts), which contribute to fibrosis and inflammation. The immune landscape is characterized by a Th1\u2010biased response, exhausted CD8\u2009+\u2009T cells and reduced regulatory T cells, with HPV infection detected in most IC\/BPS patients, suggesting a possible viral aetiology. Cell\u2010to\u2010cell interactions are compromised, with enhanced macrophage\u2010endothelial signalling via CXCL8\u2010ACKR1 and CXCL2\/3\u2010ACKR1 pathways, highlighting potential therapeutic targets. Notably, sex\u2010based differences reveal stronger immune activation in females and increased urothelial proliferation in males, potentially explaining the higher IC\/BPS prevalence in females.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>scRNA\u2010seq has advanced our understanding of IC\/BPS by identifying disease\u2010associated cell types, signalling pathways and intercellular interactions. Future research should integrate multi\u2010omics approaches and explore non\u2010invasive urine\u2010based scRNA\u2010seq for improved diagnosis and therapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bco2.70051","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T06:36:43Z","timestamp":1754375803000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["New insights into interstitial cystitis\/bladder pain syndrome at single\u2010cell resolution"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4749-594X","authenticated-orcid":false,"given":"Tadeja","family":"Kuret","sequence":"first","affiliation":[{"name":"Institute of Cell Biology, Faculty of Medicine University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6486-165X","authenticated-orcid":false,"given":"Mateja 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