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The processes of membrane fusion and reshaping of subcellular organelles are disturbed in some types of endocrine disorders and mucolipidoses such as mucolipidosis Ⅳ (MLⅣ).This is a devastating neurological disorder.It is caused by mutations affecting the protein TRPML1.The cells of MLⅣ patients contain enlarged lysosomes and accumulation of lipid materials inside them.We found disturbed Ca2+ signaling and defective late endosomes and lysosomes (LEL) in these cells.The fusion between LEL vesicles and their trafficking are also impaired.The TRPML1 channels could play a key role in Ca2+ release from LEL vesicles, which triggers the fusion, fission and trafficking of these organelles.The characterization of these processes should provide new insights into the pathophysiological mechanisms that lead to the development of MLⅣ and other lysosomal storage disorders (LSD) and neurodegenerative diseases associated with similar disturbances in dynamic membrane remodeling.In recent studies we obtained evidence suggesting that TRPML 1 may function not only as an ion channel but also as a phospholipase.It is able to cleave phospholipids in membrane bilayers and thus represents a novel type of multifunctional protein.Remarkably, the enzyme activity appears to determine its ability to generate nanotubular extensions.In cells expressing normal levels of TRPML 1 there is an extensive network of such long thin processes.We showed that these structures are deficient in cells from patients with MLⅣ.This finding suggests that TRPML1 could play an important role in membrane bending, fusion and reshaping of these extensions.We found normal formation of intercellular nanobridges and transport of subcellular vesicles along them in cells from healthy subjects but this process is deficient in MLⅣ.Thus with its multifunctional characteristics TRPML 1 can modulate the dynamic remodeling of these unique networks of tubulo-vesicular extensions and may play an important role in neurite outgrowth.This and related processes are also disturbed in severe forms of LSD and related neurodegenerative disorders.Our studies indicate that new combinations of hormonal and lipid metabolic agents may have beneficial effects for treatment of some of these disorders.