{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSURF4 functions as an integral endoplasmic reticulum (ER)‐resident cargo receptor that plays a central role in lipoprotein metabolism. By selectively recruiting apolipoprotein‐containing cargos and PCSK9 into COPII vesicles for secretion, SURF4 critically governs the assembly and export of very low‐density lipoproteins (VLDL) and related lipid particles. Hepatic disruption or knockdown of SURF4 markedly reduces plasma levels of cholesterol, triglycerides, and apolipoprotein B while protecting against atherosclerosis—all without causing overt liver damage. Furthermore, emerging evidence supports its involvement in intestinal lipid absorption and chylomicron secretion, underlying its broad role in systemic lipid homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to modulating lipid transport, SURF4 associates with STIM1 in the ER to regulate store‐operated calcium entry (SOCE) in immune cells. By influencing the clustering and function of STIM1 upon Ca²⁺ store depletion, SURF4 acts as a modulatory factor in calcium signaling pathways, which are critical for diverse cellular responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in lipid secretion and calcium dynamics, SURF4 has emerged as a multifunctional protein with implications in cell transformation and reprogramming. Elevated expression and gene amplification of SURF4 have been correlated with enhanced cell proliferation, migration, and oncogenic potential in tumor models. Moreover, as a maternal factor, SURF4 can facilitate the generation of induced pluripotent stem cells, suggesting a broader influence on cellular plasticity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xiao Wang, Huimin Wang, Bolin Xu, et al. 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