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Here, we constructed a proteomic map from thirteen anatomical brain regions of eight cadaver donors to elucidate region-specific protein expression patterns and their implications for brain function. The results underscore the interconnectivity of the four cerebral lobes, suggesting facilitated information integration through large-scale neural networks. We propose a three-module framework (cortical integration module [frontal lobe, temporal lobe, parietal lobe, occipital lobe], limbic-relay network [amygdaloid nucleus, hippocampus, thalamus\/hypothalamus], and midline regulatory axis [thalamus\/hypothalamus, corpus callosum, ventricles, optic chiasm]) and provide molecular evidence supporting the potential involvement of the midline regulatory axis, brainstem, and cerebellum in higher-order cognitive functions. The midline regulatory axis may play a critical but underexplored role in neurodevelopment, interregional signaling, and structural homeostasis, potentially through efficient synaptic function, energy metabolism, and extracellular matrix integrity. This analysis may enhance the understanding of brain physiology and highlight the need to integrate proteomic and transcriptomic approaches in the study of brain function and neurological disorders.<\/jats:p>","DOI":"10.1038\/s41392-025-02554-8","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:03:34Z","timestamp":1770163414000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Region-resolved proteomic map of the human brain: functional interconnections and neurological implications"],"prefix":"10.1038","volume":"11","author":[{"given":"Pei-Pei","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0778-0965","authenticated-orcid":false,"given":"Man-Sheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chu-Hong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Cheng","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4689-9141","authenticated-orcid":false,"given":"Xiao-Hong","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0699-8401","authenticated-orcid":false,"given":"Yi-Fang","family":"Ping","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Fang","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le-Yong","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Si","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8934-922X","authenticated-orcid":false,"given":"Jie","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Ping","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4383-0197","authenticated-orcid":false,"given":"Xiu-Wu","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6519-012X","authenticated-orcid":false,"given":"Ling","family":"Leng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"2554_CR1","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1159\/000437413","volume":"86","author":"S Herculano-Houzel","year":"2015","unstructured":"Herculano-Houzel, S., Catania, K., Manger, P. 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