LAMP2

LAMP2 Full Name

lysosomal-associated membrane protein 2

LAMP2 Introduction

LAMP2 is a heavily glycosylated type I transmembrane protein. Its core polypeptide has a molecular weight of approximately 40–45 kDa, which increases to about 120 kDa in its mature, glycosylated form. It is the most abundant protein component of the lysosomal membrane, accounting for roughly 50% of its total protein content. Composed of 417 amino acids, LAMP2 features an N-terminal luminal domain, a single transmembrane region, and a C-terminal cytoplasmic tail. The LAMP2 gene is located on the long arm of the X chromosome (Xq24) and undergoes alternative splicing to produce three main isoforms: LAMP2A, LAMP2B, and LAMP2C. Within the cell, LAMP2 is primarily localized to the lysosomal membrane, but under specific physiological or pathological conditions, it can also be recruited to late endosomes, autophagosomes, and even the plasma membrane, demonstrating a dynamic distribution.

Figure 1. Schematic drawing of the structure of human LAMP2. (Source: Qiao L, et al. 2023)

The core physiological function of LAMP2 is to maintain lysosomal structural integrity. Its extensive glycosylation forms a protective layer that shields the lysosomal membrane from degradation by the hydrolytic enzymes within the lumen. Recent research has revealed a more active role for LAMP2 in the autophagy pathway: it not only mediates the fusion of autophagosomes with lysosomes but also serves as a key receptor for chaperone-mediated autophagy (CMA). Specifically, the LAMP2A isoform recognizes substrate proteins and facilitates their translocation across the membrane, while LAMP2B and LAMP2C are involved in endosomal sorting and immune response regulation, respectively.

Genetic defects in LAMP2 directly cause Danon disease, an X-linked dominant disorder resulting from loss-of-function mutations in the LAMP2 gene. The clinical presentation classically includes a triad of hypertrophic cardiomyopathy, skeletal myopathy, and intellectual disability, with male patients typically exhibiting more severe symptoms. Beyond this monogenic disease, dysregulated LAMP2 expression is associated with various complex disorders. In the tumor microenvironment, its expression level can influence autophagic flux and chemoresistance in cancer cells. Furthermore, aberrant LAMP2 expression in models of atherosclerosis or neurodegenerative diseases suggests that impaired lysosomal function may contribute to disease progression.

Alternate Names for LAMP2

LAMP2; lysosomal-associated membrane protein 2; LAMPB; CD107b; LAMP-2; LGP110; lysosome-associated membrane glycoprotein 2; CD107 antigen-like family member B;

• 1. Qiao L, et al. LAMP2A, LAMP2B and LAMP2C: similar structures, divergent roles. Autophagy. 2023 Nov;19(11):2837-2852.
  2. Shalata A, et al. Danon Disease: Entire LAMP2 Gene Deletion with Unusual Clinical Presentation-Case Report and Review of the Literature. Genes (Basel). 2023 Jul 27;14(8):1539.