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While AMs exhibit remarkable plasticity shaped by dynamic microenvironmental cues, the traditional M1\/M2 paradigm fails to adequately capture this complex heterogeneity, and the specific role of AMs in the pathogenesis of pulmonary diseases, as well as AM\u2010centric therapies, remain to be fully elucidated. This review systematically synthesizes the current understanding of AM ontogeny, homeostatic regulation, and their signaling pathways in lung homeostasis and pathologies. Furthermore, we propose a refined conceptual framework categorizing AMs into five distinct functional subtypes to better capture their in vivo plasticity. Then, pathological shifts in the lung microenvironment that drive the pathogenesis of diverse pulmonary disorders, including asthma, chronic obstructive pulmonary disease, acute lung injury, and pulmonary fibrosis, and trigger dysregulated transcriptional and metabolic reprogramming in AMs, are comprehensively discussed. Finally, we explore emerging therapeutic avenues, including metabolic modulation, trained immunity, and autophagy\u2013apoptosis balance restoration. By addressing challenges in precisely regulating AM function, this overview provides a concise yet comprehensive framework for advancing AM\u2010centric therapies in respiratory medicine.<\/jats:p>","DOI":"10.1002\/mco2.71031","type":"journal-article","created":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T08:06:00Z","timestamp":1791101160000},"source":"Crossref","is-referenced-by-count":0,"title":["Alveolar Macrophages: Development, Respiratory Homeostasis, Signal Pathways, Diseases, and Therapeutic Opportunities"],"prefix":"10.1002","volume":"7","author":[{"given":"Sihan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Biotherapy and Division of Infectious Diseases Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University  Chengdu China"},{"name":"State Key Laboratory of Oral Diseases National Clinical Research Center for Oral Diseases Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and 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