P4‐ATPases as Phospholipid Flippases: From Membrane Dynamics to Human Disorders

ABSTRACT P4‐ATPases (P4 subfamily of P‐type ATPases) flippase complex includes an α ‐subunit responsible for catalysis and a supporting β ‐subunit, which consumes energy by catalyzing the hydrolysis of ATP, thereby facilitating the translocation of aminophospholipids from the outer to the inner leaflet of cellular membranes to maintain the asymmetric distribution of phospholipids. This mechanism plays a vital role in numerous physiological and biochemical processes, such as cellular signal transduction, membrane fusion, neurotransmission, immune responses, cell cycle regulation, and platelet activation. Emerging evidence relates P4‐ATPases to various pathological conditions. Here, we outline the latest findings on the physiological roles of P4‐ATPases and their potential link to human diseases, with a particular focus on the underlying mechanisms by which these flippase contribute to disease pathogenesis.