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This article synthesizes recent advances in genetics, transcriptomics, and physiology to elucidate how AR  mutations drive tissue-specific metabolic reprogramming in key organs, including pancreatic \u03b2-cells, skeletal muscle, liver, and adipose tissue. Particular attention is given to a newly identified familial AR  variant (c.2117A&gt;G; p.Asn706Ser), which not only broadens the known mutational spectrum of AIS but also underscores the clinical importance of early metabolic risk screening in this population. We further examine how pubertal stage, hormone replacement therapy, and sex-specific signaling pathways interact to influence long-term metabolic outcomes. Lastly, we propose an integrative management framework that incorporates genetic diagnosis, endocrine surveillance, and personalized pharmacological strategies aimed at reducing the risk of type 2 diabetes mellitus and cardiometabolic complications in individuals with AIS. Distinct from previous AIS-centered reviews, this work integrates metabolic and endocrine perspectives into the traditional developmental paradigm, offering a more comprehensive understanding of disease risk and translational management.<\/jats:p>","DOI":"10.4239\/wjd.v16.i11.112236","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T02:10:51Z","timestamp":1763086251000},"source":"Crossref","is-referenced-by-count":1,"title":["Androgen receptor mutations in familial androgen insensitivity syndrome: A metabolic reprogramming pathway to type 2 diabetes 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