EEIG2

EEIG2 (FAM102B) functions as an adaptor protein at ER–plasma membrane contact sites, where it mediates recruitment of the bridge-like lipid transfer protein BLTP2 to the plasma membrane alongside phosphoinositides and N-BAR domain proteins (PMID:40899996). Through this interaction, EEIG2 contributes to ER tethering to the plasma membrane, supporting membrane contact at sites of bulk lipid transport (PMID:40899996). Beyond its role as a BLTP2 adaptor at these contact sites, no further mechanistic detail for EEIG2 has been characterized in the available corpus.

1. 2025 Medium

   Whether FAM102B/EEIG2 had a defined molecular role was unknown; identifying it as a BLTP2 binding partner at ER-PM contacts established it as an adaptor coupling a bridge-like lipid transfer protein to the plasma membrane.

   Evidence Interaction mapping and localization in cell-based systems, with loss-of-function showing PM-connected intracellular vacuole accumulation (peer-reviewed)

   PMID:40899996

   Open questions at the time

   • No orthogonal validation (mutagenesis or reconstitution) for the FAM102B-BLTP2 interaction specifically
   • Vacuole accumulation phenotype attributed to BLTP2 loss, not directly to FAM102B loss
   • Mechanism by which FAM102B engages the PM (lipid vs protein determinants) not defined
2. 2025 Medium

   The preprint extended the adaptor model by placing FAM102B-mediated BLTP2 tethering at tubular endosomes continuous with the PM and at macropinosomes fusing with the PM, broadening the membrane contexts where it operates.

   Evidence Interaction mapping and localization in cell-based systems (preprint)

   PMID:39974967

   Open questions at the time

   • Preprint without detailed orthogonal validation for FAM102B
   • Direct demonstration of lipid transport dependence on FAM102B not shown
   • Stoichiometry and structural basis of the BLTP2 interaction unresolved

• How FAM102B selects and stabilizes specific contact-site geometries, and whether its adaptor function is required for bulk lipid transport itself, remains open.
• No direct loss-of-function phenotype attributed specifically to FAM102B
• No structural or biochemical reconstitution of the FAM102B-BLTP2-PM assembly
• Physiological consequences of FAM102B loss at the organism level uncharacterized