EFR3B is a lipidated peripheral membrane protein that serves as the membrane-anchoring component of a complex essential for plasma membrane recruitment of phosphatidylinositol 4-kinase (PI4KA) 1. EFR3B functions as part of a heterotrimeric complex with PI4KA and its regulatory proteins TTC7B and FAM126A 2. The EFR3B C-terminus directly interacts with both TTC7B and FAM126A, facilitating PI4KA localization to the plasma membrane where it regulates phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis 1. EFR3B phosphorylation markedly decreases its binding affinity to TTC7-FAM126 complexes, providing a mechanism for dynamic regulation 3. Beyond lipid signaling, EFR3B participates in G-protein-coupled receptor responsiveness, though the mechanism remains unclear 4. Disease-linked mutations at the EFR3B-PI4KA interaction interface disrupt complex formation and membrane recruitment 5. EFR3B has been identified as a potential biomarker in glioma pathogenesis 6 and may contribute to osteoporosis development 7. The identification of selective nanobodies blocking EFR3B-mediated PI4KA recruitment provides therapeutic tools for manipulating this critical signaling complex 3.