Lysosome-associated membrane glycoprotein 2a (LAMP-2A)

Lysosome-associated membrane glycoprotein 2a (LAMP-2A) is a transmembrane glycoprotein integral to the lysosomal membrane and serves as the essential receptor and channel for chaperone-mediated autophagy (CMA), a selective autophagy pathway responsible for importing specific cytosolic proteins into the lysosome for degradation[2][1][3][4]. LAMP-2A recognizes substrates in the cytosol (tagged by chaperones) via its short cytosolic tail and facilitates their translocation across the membrane, thereby regulating cell proteostasis and quality control[1][4]. Dysregulation or deficiency of LAMP-2A impairs CMA, contributing to various diseases, including neurodegenerative diseases and certain cancers[4][3]. LAMP-2A has distinct isoforms (LAMP-2B and LAMP-2C) with largely non-overlapping functions, but only LAMP-2A confers chaperone-mediated autophagy receptor activity[2][3][4]. There are currently no clinically approved drugs that specifically target LAMP-2A, but it remains an area of active investigation as a therapeutic target in aging, cancer, and proteinopathy-related diseases[4].

Other names

LAMP2ALAMP2-ACD107b (isoform-specific context)Chaperone-mediated autophagy receptorLysosome-associated membrane protein 2a

Modulation of chaperone-mediated autophagy through regulating substrate (protein) translocation into lysosome - Inhibition or enhancement of CMA flux