SEC24C is a key component of the COPII vesicle coat complex that mediates protein transport from the endoplasmic reticulum (ER) to the Golgi apparatus 1. As part of the COPII machinery, SEC24C plays essential roles in cargo selection and packaging, with distinct cargo specificities compared to other SEC24 paralogs 1. The protein undergoes dynamic post-translational modifications during cell cycle progression, including O-GlcNAcylation in interphase that is removed during mitosis to regulate its cellular localization 2. SEC24C is crucial for maintaining ER tubule junctions and facilitating selective ER autophagy (reticulophagy), working with RTN3L to target misfolded proteins for degradation 3. The protein also serves as a host dependency factor for HIV-1 infection, directly binding to viral capsid lattices through its FG-motif and facilitating viral trafficking, core stability, and infectivity 45. Clinically, SEC24C deficiency causes severe developmental disorders including epileptic encephalopathy, microcephaly, and multiple organ dysfunction 1, while acquired mutations in SEC24C contribute to resistance to immune checkpoint inhibitors in melanoma by disrupting STING signaling 6. These findings establish SEC24C as critical for both normal cellular trafficking and pathological processes involving viral infection and cancer treatment resistance.