9.B.39.1.13
Lysosomal integral membrane homodimeric protein 2, LIMP2. SCARB2, CD36L2, or LIMPII, of 478 aas and two TMSs at the N- and C-termini. It acts as a lysosomal receptor for glucosylceramidase (GBA) targeting (Reczek et al. 2007) as well as a receptor for enterovirus 71 (Yamayoshi et al. 2009; Zhou et al. 2019). It plays a role in the activation of autophagy (Sakane et al. 2020). It also functions in aminophospholipid transport and is part of lysosome-endoplasmic reticulum STARD3-VAPB-dependent contact sites (Rudnik et al. 2024). LIMP-2 functions as a virus receptor (see above), a chaperone for lysosomal enzyme targeting, and a lipid transporter. The large luminal domain of LIMP-2 contains a hydrophobic tunnel that enables transport of phospholipids, sphingosine and cholesterol from the lysosomal lumen to the membrane (Rudnik et al. 2024). It interacts with the endosomal protein STARD3 and the ER-resident protein VAPB. Colocalization and physical interaction between LIMP-2 and these proteins has been demonstrated. Moreover, interaction of LIMP-2 with VAPB required the presence of STARD3. Thus, LIMP-2 is part of ER-lysosome contact sites, possibly facilitating cholesterol transport from the lysosomal to the ER membrane, possibly a novel mechanism for inter-organelle communication and lipid trafficking mediated by LIMP-2.