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Although the biochemistry of lipid synthesis and degradation is well characterized, the regulation of LD dynamics, including its formation, maintenance, and secretion, is poorly understood. Here, we report that mice lacking\n                    <jats:italic>Occludin<\/jats:italic>\n                    (\n                    <jats:italic>Ocln<\/jats:italic>\n                    ) show defective lipid metabolism. We show that LDs were larger than normal along its biogenesis and secretion pathway in\n                    <jats:italic>Ocln<\/jats:italic>\n                    null mammary cells. This defect in LD size control did not result from abnormal lipid synthesis or degradation; rather, it was because of secretion failure during the lactation stage. We found that OCLN was located on the LD membrane and was bound to essential regulators of lipid secretion, including BTN1a1 and XOR, in a C-terminus\u2013dependent manner. Finally, OCLN was a phosphorylation target of Src kinase, whose loss causes lactation failure. Together, we demonstrate that\n                    <jats:italic>Ocln<\/jats:italic>\n                    is a downstream target of Src kinase and promotes LD secretion by binding to BTN1a1 and XOR.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3001518","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T14:59:01Z","timestamp":1642517941000},"page":"e3001518","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Occludin is a target of Src kinase and promotes lipid secretion by binding to BTN1a1 and 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