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In mosquitoes and other insects, the olfactory system detects environmental odors primarily through a diverse repertoire of odorant receptors (ORs), which require the highly conserved odorant receptor co-receptor (\n                    <jats:italic>Orco<\/jats:italic>\n                    ) to function. While\n                    <jats:italic>Orco\u2019<\/jats:italic>\n                    s role in enabling receptor function is well established, its cellular localization patterns, developmental expression dynamics, and system-wide impact on olfactory physiology and behavior remain understudied in\n                    <jats:italic>Ae. albopictus<\/jats:italic>\n                    . To address this knowledge gap, we leveraged the Q-system to systematically characterize\n                    <jats:italic>Orco<\/jats:italic>\n                    -expressing neurons across embryonic, larval, and adult stages of\n                    <jats:italic>Ae. albopictus<\/jats:italic>\n                    .\n                    <jats:italic>Orco<\/jats:italic>\n                    -expressing neurons were observed as early as in the embryonic stage and proliferated during larval development.\n                    <jats:italic>Orco<\/jats:italic>\n                    expression in adults spanned the olfactory sensory neurons (OSNs)\u00a0of the antennae, labella, and maxillary palps in both male and female mosquitoes, consistent with its conserved peripheral distribution across various mosquito species. To further investigate the functional implications of\n                    <jats:italic>Orco<\/jats:italic>\n                    , we generated\n                    <jats:italic>Orco<\/jats:italic>\n                    knockout mutants and strikingly discovered that\n                    <jats:italic>Orco<\/jats:italic>\n                    knockout mutants displayed significant widespread downregulation of ORs, suggesting that\n                    <jats:italic>Orco<\/jats:italic>\n                    may influence ORs\u2019 expression or stability. Electrophysiological recordings confirmed significantly attenuated responses to human volatiles in\n                    <jats:italic>Orco<\/jats:italic>\n                    mutants, and behavioral assays demonstrated a marked decline in blood-feeding efficiency and decrease of human preference in females. Together, these findings reveal dynamic organization of OSNs during mosquito development and uncover the critical role of\n                    <jats:italic>Orco<\/jats:italic>\n                    in maintaining the integrity and function of the olfactory system, providing insights which may inform novel, next-generation vector control strategies.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0013753","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T18:42:07Z","timestamp":1764182527000},"page":"e0013753","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Unveiling the developmental dynamics and functional role of Odorant Receptor Co-receptor (Orco) in Aedes albopictus: A novel mechanism for regulating odorant receptor 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