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Mitochondria-associated membranes (MAMs) are the organellar contact sites between mitochondria and the endoplasmic reticulum (ER), and recent studies demonstrated that MAMs, which serve as multiple scaffolds of proteins, are involved in Ca2+ signaling, lipid metabolism, mitochondrial morphology and functions, and autophagy. Importantly, several pathological conditions, such as obesity, diabetes mellitus and neurodegenerative diseases, indicate the significant role of MAMs in cellular homeostasis. Phosphofurin acidic cluster sorting protein 2(PACS-2), a multifunctional sorting protein at MAMs, plays a critical role in mitochondria, ER and lysosome homeostasis. In this review, we summarize the current understanding of the role of PACS-2 as a key regulator of MAMs and present the structure and other functions of PACS-2. Moreover, we describe the relationship between PACS-2 and diseases to reveal its potential as a novel therapeutic target that can be applied for the treatment of diseases.
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