Emerging evidence highlights that the temporary loss of plasma membrane lipid asymmetry plays a critical role in maintaining normal physiological functions. For instance, recent studies reveal that plasma membrane SM asymmetry is disrupted during lysosomal damage . Calcium release from damaged lysosomes activates SM scramblase, flipping SM to the cytosolic leaflet, which converts it into ceramide. This ceramide facilitates lysosomal repair through an ESCRT-independent pathway.