LAMP2A, LAMP2B and LAMP2C: similar structures, divergent roles

LAMP2 (lysosomal associated membrane protein 2) is one of the major protein components of the lysosomal membrane. There currently exist three LAMP2 isoforms, LAMP2A, LAMP2B and LAMP2C, and they vary in distribution and function. LAMP2A serves as a receptor and channel for transporting cytosolic proteins in a process called chaperone-mediated autophagy (CMA). LAMP2B is required for autophagosome-lysosome fusion in cardiomyocytes and is one of the components of exosome membranes. LAMP2C is primarily implicated in a novel type of autophagy in which nucleic acids are taken up into lysosomes for degradation. In this review, the current evidence for the function of each LAMP2 isoform in various pathophysiological processes and human diseases, as well as their possible mechanisms, are comprehensively summarized. We discuss the evolutionary patterns of the three isoforms in vertebrates and provide technical guidance on investigating these isoforms. We are also concerned with the newly arising questions in this particular research area that remain unanswered. Advances in the functions of the three LAMP2 isoforms will uncover new links between lysosomal dysfunction, autophagy and human diseases.

Automated summary

LAMP2 is a major protein component of the lysosomal membrane and has three isoforms, LAMP2A, LAMP2B, and LAMP2C, with different distribution and functions. LAMP2A acts as a receptor and channel for transporting cytosolic proteins in chaperone-mediated autophagy. LAMP2B is involved in autophagosome-lysosome fusion and is a component of exosome membranes. LAMP2C participates in a novel type of autophagy that degrades nucleic acids in lysosomes. This review provides a comprehensive summary of the functions and mechanisms of each LAMP2 isoform in various pathophysiological processes and human diseases. The evolutionary patterns of these isoforms in vertebrates are discussed, along with technical guidance for investigating them. Unanswered questions in this research area are also highlighted. Advances in understanding the functions of the three LAMP2 isoforms will reveal new connections between lysosomal dysfunction, autophagy, and human diseases.