2.A.74.1.3
Lysosomal-associated transmembrane protein 4-beta, LAPTM4B of 317 aas and 4 TMSs.  Upregulated in many types of cancer cells, in part accounting for multidrug resistance.  Associates with P-Glycoprotein (Li et al. 2010).  May be able to flip lipids from the inner leaflet of the membrane to the outer leaflet, thereby promoting programmed cell death (Blom et al. 2015). This late endosomal protein  controls amino acid transporter interactions (Zhou et al. 2018). The ceramide-mediated regulation of LAPTM4B depends on a sphingolipid interaction motif and an adjacent aspartate residue in the protein's third transmembrane (TMS3) helix. This facilitates the interaction between LAPTM4B and the amino acid transporter heavy chain 4F2hc, thereby controlling mTORC signaling (Zhou et al. 2018). LAPTM4B regulates ceramide-induced exosome release  (Yuyama et al. 2020). (Exosomes are extracellular vesicles that mediate the transport of intracellular molecules, including neurodegenerative agents, and exogenously administrated ceramides, especially those consisting of long fatty acids, accelerate exosome production by neurons and neuroblastoma cells, inducing exosome secretion through LAPTM4B.) LAPTM4B regulates ceramide-induced exosome release (Yuyama et al. 2020) and regulates amino acid transport interactions (Zhou et al. 2018). For example, it recruits the LAT1-4F2hc Leu transporter to lysosomes (Milkereit et al. 2015). It may also facilitate late endosomal ceramide export to control cell death pathways (Blom et al. 2015). Serum LAPTM4B is a potential diagnostic and prognostic biomarker for breast cancer (Wang et al. 2022). It counteracts ferroptosis by suppressing the ubiquitin-proteasome degradation of SLC7A11 (TC# 2.A.3.8.18) in non-small cell lung cancer (Yan et al. 2024).