{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTMEM30A, also known as CDC50A, functions as an indispensable β‐subunit for P4‐ATPase flippase complexes that actively translocate aminophospholipids—particularly phosphatidylserine (PS)—from the outer to the inner leaflet of the plasma membrane. This lipid asymmetry is crucial for maintaining membrane homeostasis, proper membrane dynamics, and signaling processes. Its role in ensuring the correct folding, stabilization, and export of associated P4‐ATPases has been demonstrated in studies investigating liver cholestasis, phospholipid uptake, and cell surface distribution of bioactive lipids."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTMEM30A is also critically involved in regulating cell membrane PS exposure, a key “eat‐me” signal in apoptotic cell clearance and in the uptake of exogenous phospholipids that can influence chemotherapeutic efficacy. For example, in apoptotic cells whose flippase activity is disrupted, loss of functional TMEM30A/CDC50A has been linked to abnormal PS externalization and subsequent phagocytic removal, and its deficiency can lead to increased accumulation of anticancer lipid mimetics in malignant cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nHigh-resolution structural and mutational analyses have provided detailed insights into how TMEM30A supports P4‐ATPase function. Such studies reveal that TMEM30A not only ensures proper complex formation with P4‐ATPases (thereby enabling phospholipid transport through well‐defined transmembrane crevices) but also is necessary for inducing the lipid-stimulated ATPase activity of these enzymes."}, {"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 classical role in lipid translocation, TMEM30A has been implicated in diverse cellular contexts. In neuronal and endosomal systems, TMEM30A interacts with the β‐carboxyl-terminal fragment of amyloid precursor protein, suggesting a mechanistic link to endosomal trafficking defects that may underlie Alzheimer’s disease pathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Moreover, in the vascular system, TMEM30A is critical for retinal angiogenesis, where its loss in endothelial cells results in impaired vessel growth and barrier function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTMEM30A’s broader physiological significance is underscored by its emerging roles in other disease contexts. A non‐coding circular RNA derived from TMEM30A (CircTMEM30A) has been associated with the pathogenesis of chronic obstructive pulmonary disease and lung cancer, while TMEM30A is essential in preserving podocyte integrity and glomerular filtration in the kidney. In muscle cells, deletion of TMEM30A impairs myoblast fusion by disrupting actin remodeling and small GTPase targeting, and in hematological malignancies, loss of TMEM30A alters PS exposure at the cell surface to modulate natural killer cell recognition and killing. Together, these findings demonstrate that TMEM30A is a multifaceted regulator whose functions extend from basic maintenance of membrane lipid asymmetry to the modulation of cell signaling and intercellular communications in health and disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Coen C Paulusma, Dineke E Folmer, Kam S Ho-Mok, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "CDC50A plays a key role in the uptake of the anticancer drug perifosine in human carcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Pharmacol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bcp.2010.05.017"}], "href": "https://doi.org/10.1016/j.bcp.2010.05.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20510206"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20510206"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Rui Chen, Erin Brady, Thomas M McIntyre "}, {"type": "b", "children": [{"type": "t", "text": "Human TMEM30a promotes uptake of antitumor and bioactive choline phospholipids into mammalian cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1002710"}], "href": "https://doi.org/10.4049/jimmunol.1002710"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21289302"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21289302"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Utako Kato, Hironori Inadome, Masatoshi Yamamoto, et al. 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