GCC2 (GRIP and coiled-coil domain containing 2) is a trans-Golgi network (TGN) golgin that functions as a vesicle tether regulating intracellular transport 1. As a RAB9A effector, GCC2 mediates mannose 6-phosphate receptor (M6PR) recycling from late endosomes to the TGN and facilitates Golgi-endosome transport 2. GCC2 is essential for Golgi structural integrity and recruits microtubule-organizing proteins to maintain noncentrosomal Golgi-associated microtubules 1. Recently, GCC2 was identified on lytic granule surfaces in cytotoxic immune cells, where it tethers granules to the Golgi following convergence at the MTOC, preventing off-target killing 3. Clinically, GCC2 variants cause human natural killer cell deficiency associated with impaired immune precision 3. In non-small cell lung cancer (NSCLC), GCC2 is aberrantly overexpressed and promotes progression by maintaining Golgi integrity and enhancing EGFR signaling 1. Exosomal GCC2 serves as an early diagnostic biomarker for NSCLC with 90% sensitivity and 75% specificity 4. Additionally, GCC2 participates in oncogenic fusion proteins (GCC2-PDGFRB, GCC2-ALK) associated with hematologic and lung malignancies responsive to targeted inhibitors [PMID:30697976; 52]. GCC2 regulation also influences TGF-β1 signaling in transplant immunology, affecting kidney allograft outcomes 6.