Pathway to hemolysis. (A) High membrane tension activates Piezo1, and the uptake of Ca⁺⁺ activates the Gardos channel. (B) Ca⁺⁺ activation of CaM and PKC leads to disruption of the skeleton-membrane connectivity. (C) Calpain degrades ankyrin, causing skeleton-membrane disruption. PS, phosphatidylserine; SC, suspension complex.