Progress on multifunctional transmembrane protein ATG9A.

ATG9A is the only transmembrane protein among the components required for autophagosome formation and participates in multiple cellular biological processes. ATG9A undergoes intracellular transport via microtubules and actin. As a lipid scramblase, ATG9A facilitates the random movement of lipid molecules between the inner and outer leaflets of lipid bilayers. Additionally, it can influence the homeostasis of the plasma membrane and membranous organelles. In autophagy, ATG9A is recruited to autophagic initiation sites to initiate cellular autophagy and subsequently participates in the process by promoting lipid transfer. Moreover, ATG9A also plays roles in maintaining neuronal homeostasis and is involved in embryonic development, infection, and immune responses. In this review, we comprehensively and systematically summarize the roles and mechanisms of ATG9A, aiming to provide a new perspective for understanding its functions.