{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n MAN2B2 encodes a lysosomal mannosidase—specifically, a core α‑1,6‐mannosidase—that plays a critical role in the degradation and processing of N‑glycans. Functional studies have demonstrated that, along with its paralog MAN2B1, MAN2B2 (also referred to as hEpman in human studies) acts on distinct glycosidic linkages in the lysosome to mediate glycan breakdown."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Its enzymatic properties, including sensitivity to specific mannosidase inhibitors and distinct metal‐dependency characteristics, underscore its specialized catalytic function in glycoprotein turnover.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Clinically, loss‐of‐function of MAN2B2 has been associated with a complex multisystem phenotype characterized by immune dysregulation, developmental delay, and stroke; importantly, restoration of normal mannosylation in patient cells was achieved by reintroducing the wild‑type enzyme."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In livestock, particularly in swine, genetic studies have positioned MAN2B2 as a strong candidate influencing reproductive traits. In pig populations, both association mapping and quantitative trait locus (QTL) analyses have revealed that single nucleotide polymorphisms in MAN2B2 are significantly associated with ovulation rate and, as a consequence, litter size, supporting a role for proper glycosylation in reproductive physiology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, comparative expression analysis in primate brains has shown that MAN2B2 is expressed at significantly higher levels in the human left cerebrum compared to that of chimpanzees, suggesting that differences in MAN2B2‐mediated glycan metabolism may contribute to species‑specific metabolic or regulatory networks."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Additional studies in the epididymis have detected MAN2B2 as one of at least two distinct α‑D‑mannosidases present in the luminal fluid. In porcine models, the 135‑kDa MAN2B2 protein is specifically expressed in certain epididymal regions, hinting at a role in the glycoprotein modification events that accompany sperm maturation and regional differentiation within the epididymis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, MAN2B2 serves as a key lysosomal enzyme for the breakdown of N‑glycans, and its proper activity is essential for normal cellular glycoprotein processing. Its dysfunction or genetic variation can have wide‐ranging effects, from contributing to developmental and immune disorders in humans to influencing reproductive efficiency in livestock, while also potentially underpinning species‑specific metabolic differences.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Meenakshi Venkatesan, Douglas A Kuntz, David R Rose "}, {"type": "b", "children": [{"type": "t", "text": "Human lysosomal alpha-mannosidases exhibit different inhibition and metal binding properties."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Protein Sci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pro.235"}], "href": "https://doi.org/10.1002/pro.235"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19722277"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19722277"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jan Verheijen, Sunnie Y Wong, Jared H Rowe, et al. 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