{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC16A7, which encodes the monocarboxylate transporter 2 (MCT2), is a high‐affinity mediator of the bidirectional exchange of key monocarboxylates—such as lactate, pyruvate, ketone bodies, and even gamma‐hydroxybutyrate—thereby playing a central role in cellular energy homeostasis. Developmental studies in the human visual cortex have revealed early neuronal expression of MCT2 that supports metabolic demands during maturation, while analyses in various normal and tumor tissues demonstrate that its activity is finely tuned by contextual cues. For example, MCT2 shows altered localization in colorectal carcinomas, with decreased plasma membrane presence, and its expression is modulated by hypoxic conditions in adipocytes. Moreover, in several neoplasms including breast and prostate cancers, MCT2 contributes to the regulation of intracellular pH and metabolic reprogramming, with extracellular factors such as non‐catalytic CAIV further enhancing its transport activity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn disease contexts, disruptions in MCT2 function and expression have been linked to pathological metabolic reprogramming. In colorectal and prostate cancers, for instance, aberrant expression patterns—including mislocalization from the plasma membrane and, in some cases, peroxisomal targeting—are associated with increased beta‐oxidation and enhanced tumorigenic potential. Epigenetic alterations, such as selective promoter demethylation within the SLC16A7 locus, lead to the expression of distinct 5′‐UTR isoforms that may underlie MCT2 overexpression and have been correlated with tumor growth. In addition, single nucleotide polymorphisms in MCT2 have been implicated in modulating clinical outcomes in cancers such as colorectal and lung neoplasms, and variants in this gene are also associated with altered sperm MCT2 protein levels and a higher risk of male infertility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic investigations have further delineated MCT2’s unique structural and kinetic properties. Cryo‐electron microscopy studies reveal that MCT2 operates with a steep, switch‐like substrate dependence that is attributed to strong inter‐subunit cooperativity within its dimeric assembly, while conserved extracellular residues—such as a critical aspartate—mediate its pH‐dependent transport characteristics. Beyond oncology, MCT2 is integral to cerebral energy dynamics; its postsynaptic localization in the human cortex correlates with regional metabolic demand and supports the astrocyte–neuron lactate shuttle. Moreover, by facilitating the uptake of metabolites derived from prodrug hydrolysis (e.g. methyloxalylglycine), MCT2 links transporter activity to broader aspects of metabolic flux and therapeutic response."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Laurence Fayol, Olivier Baud, Anne Monier, et al. 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