**1. Introduction**

Cholesterol is an essential biomolecule, involved in a wide array of physiological and pathological processes. In the plasma membrane, changes in free cholesterol content and phospholipid species modulate signaling of multiple receptors [1]. A physiological free cholesterol/phospholipid ratio in cellular membranes is necessary to maintain membrane fluidity [2], and altered membrane fluidity adversely affects the conformation and function of certain integral membrane proteins that can be inhibited by a high free cholesterol/phospholipid ratio [3]. Excess plasma membrane cholesterol also disrupts the function of certain signaling molecules that normally reside in non-raft domains. In addition, excess intracellular cholesterol levels can also cause toxicity by mechanisms including intracellular cholesterol crystallization, oxidation of cholesterol to oxysterols and triggering of apoptotic signaling pathways [4].

One of several proteins involved in cholesterol homeostasis is the ATP-binding cassette transporter A1 (ABCA1), a transmembrane protein widely expressed in many tissues where it may have many different functions. Its most studied function is the efflux of intracellular free cholesterol and phospholipids across the plasma membrane to combine with apolipoproteins, mainly apolipoprotein A-I (ApoA-I), forming nascent high-density

**Citation:** Jacobo-Albavera, L.; Domínguez-Pérez, M.; Medina-Leyte, D.J.; González-Garrido, A.; Villarreal-Molina, T. The Role of the ATP-Binding Cassette A1 (ABCA1) in Human Disease. *Int. J. Mol. Sci.* **2021**, *22*, 1593. https://doi.org/10.3390/ ijms22041593

Academic Editor: Thomas Falguières Received: 31 December 2020 Accepted: 27 January 2021 Published: 5 February 2021

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lipoprotein particles (HDLs), the first step of reverse cholesterol transport (RCT) [5]. RCT is the process by which the body removes excess cholesterol from peripheral tissues and delivers this cholesterol to the liver, where it is redistributed to other tissues or removed from the body by the gallbladder. HDL-cholesterol (HDL-C) particles are the main lipoproteins involved in this process [6]. In addition to HDL-C formation, ABCA1 regulates cholesterol and phospholipid content in the plasma membrane and is involved in microparticle formation and thus in cell signaling. For all these reasons, it is not surprising that altered cholesterol homeostasis may affect many different organs and is involved in the pathophysiology of a broad array of diseases (Figure 1). The present review focuses on the role of the ABCA1 cholesterol transporter in human disease.

**Figure 1.** ATP-binding cassette transporter A1 (ABCA1) functions in different cell types and associated diseases. ABCA1 is widely expressed and participates in a broad array of physiological and pathological processes. ApoE: apolipoprotein E; HDL: high-density lipoproteins; apoAI: apolipoprotein I.
