Lysosome-associated membrane glycoprotein 2 isoform A (LAMP2A) (LAMP2A)

Lysosome-associated membrane glycoprotein 2 isoform A (LAMP2A) is a critical lysosomal membrane protein that serves as the rate-limiting receptor for chaperone-mediated autophagy (CMA) [Cuervo & Dice, 1996, Science]. Unlike macroautophagy, CMA is a selective process where specific cytosolic proteins containing a KFERQ-like motif are recognized by the chaperone Hsc70 and delivered to LAMP2A for translocation into the lysosomal lumen for degradation [Kaushik & Cuervo, 2018, Nat Rev Mol Cell Biol]. LAMP2A levels and its multimerization state at the lysosomal membrane directly determine CMA activity, making it a primary target for therapeutic intervention in proteostasis-related disorders. In neurodegenerative diseases like Parkinson's and Alzheimer's, LAMP2A expression often declines with age or is inhibited by toxic protein aggregates, leading to further accumulation of pathogenic proteins like alpha-synuclein and tau [Xilouri et al., 2013, Brain]. Conversely, many cancer cells upregulate LAMP2A to survive metabolic stress and maintain high proliferation rates, suggesting that LAMP2A inhibition may be beneficial in oncology [Kon et al., 2011, Sci Transl Med]. Current pharmacological approaches include small-molecule activators like AR7 and retinoic acid receptor alpha (RARα) antagonists that stabilize LAMP2A, as well as therapeutic peptides like P140 that modulate its activity in autoimmune contexts [Anguiano et al., 2013, Nat Chem Biol; Muller et al., 2008, Sci Transl Med].

Other names

LAMP-2ACD107bLGP110Lysosome-associated membrane protein 2 isoform A

Upregulation of LAMP2A expression, stabilization of LAMP2A protein at the lysosomal membrane, and promotion of LAMP2A multimerization to increase chaperone-mediated autophagy (CMA) flux.