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SREBP s are master regulators of lipid homeostasis and undergo sterol‐regulated export from  ER  to Golgi apparatus for processing and activation via  COPII ‐coated vesicles. While  COPII  recognizes  SREBP  through its escort protein  SCAP , factor(s) specifically promoting  SREBP / SCAP  loading to the  COPII  machinery remains unknown. Here, we show that the  ER /lipid droplet‐associated protein Cideb selectively promotes the loading of  SREBP / SCAP  into  COPII  vesicles. Sterol deprivation releases  SCAP  from Insig and enhances  ER  export of  SREBP / SCAP  by inducing  SCAP ‐Cideb interaction, thereby modulating sterol sensitivity. Moreover, Cideb binds to the guanine nucleotide exchange factor Sec12 to enrich  SCAP / SREBP  at  ER  exit sites, where assembling of  COPII  complex initiates. Loss of Cideb inhibits the cargo loading of  SREBP / SCAP , reduces  SREBP  activation, and alleviates diet‐induced hepatic steatosis. Our data point to a linchpin role of Cideb in regulated  ER  export of  SREBP  and lipid homeostasis.

Cideb controls sterol‐regulated ER export of SREBP / SCAP by promoting cargo loading at ER exit sites