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Formation of these outward budding vesicles at the plasma membrane is associated with an increase in cytosolic calcium and oxidation, as well as the disruption of the actin cytoskeletonplasma membrane interface (Pollet, Conrard, Cloos, & Tyteca, 2018), and each of these occurs locally in the immediate aftermath of membrane injury (Andrews et al., 2014; Horn & Jaiswal, 2018). Andrews NW, Almeida PE, & Corrotte M (2014). What feature of a cell membrane allows it to repair itself quickly? Thus, electrostatic interaction with signaling lipids helps to facilitate GTPase localization, which is a critical feature that determines the efficiency and magnitude of the downstream response (Das et al., 2015; Yogurtcu & Johnson, 2018). Jimenez AJ, Maiuri P, Lafaurie-Janvore J, Divoux S, Piel M, & Perez F (2014). C-terminal di-arginine motif of Cdc42 protein is essential for binding to phosphatidylinositol 4, 5-bisphosphate-containing membranes and inducing cellular transformation, Plasma membraneCortical cytoskeleton interactions: A cell biology approach with biophysical considerations, Control of diverse subcellular processes by a single multi-functional lipid phosphatidylinositol 4, 5-bisphosphate [PI (4, 5) P2], The structural role of cholesterol in cell membranes: from condensed bilayers to lipid rafts. While intracellular MG53 is a redox-sensitive protein capable of facilitating vesicle aggregation, it is proposed to have multiple functions during membrane repair. While small injuries to the plasma membrane (on the nanometer scale) can be spontaneously resealed due to the line tension imposed by plasma membrane lipids alone (McNeil & Terasaki, 2001), larger membrane injuries (on the micron scale) require a series of coordinated mechanisms to undergo repair. These roles of lipids in plasma membrane repair include both a structural role and a signaling role. Spontaneous resealing of plasma membrane, Spontaneous resealing of plasma membrane injuries in the nanometer range is opposed by, Calcium-activated exocytosis reduces membrane tension, Calcium-activated exocytosis reduces membrane tension and promotes spontaneous repair driven by lipid disorder, Very large plasma membrane disruptions (micron diameter) require membrane patching. Development of cell therapy and regenerative medicine using stem cells is expanding the medical industry and businesses as well as increasing the understanding of the nature of the cell itself. The calcium influx of a membrane injury activates vesicular exocytosis and homo- and heterotypic fusion of cytoplasmic vesicles. We here review what is known about the cellular and molecular mechanisms of membrane repair, with particular emphasis on the relevance of repair as it relates to disease pathologies. This process, facilitated by the dysferlin-mediated release of acid sphingomyelinase (Defour et al., 2014) creates microdomains of ceramide from sphingomyelin.